|
1
|
Kanai SM, Clouthier DE. Endothelin signaling in development. Development 2023; 150:dev201786. [PMID: 38078652 PMCID: PMC10753589 DOI: 10.1242/dev.201786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2023]
Abstract
Since the discovery of endothelin 1 (EDN1) in 1988, the role of endothelin ligands and their receptors in the regulation of blood pressure in normal and disease states has been extensively studied. However, endothelin signaling also plays crucial roles in the development of neural crest cell-derived tissues. Mechanisms of endothelin action during neural crest cell maturation have been deciphered using a variety of in vivo and in vitro approaches, with these studies elucidating the basis of human syndromes involving developmental differences resulting from altered endothelin signaling. In this Review, we describe the endothelin pathway and its functions during the development of neural crest-derived tissues. We also summarize how dysregulated endothelin signaling causes developmental differences and how this knowledge may lead to potential treatments for individuals with gene variants in the endothelin pathway.
Collapse
Affiliation(s)
- Stanley M. Kanai
- Department of Craniofacial Biology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
| | - David E. Clouthier
- Department of Craniofacial Biology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
| |
Collapse
|
|
2
|
Maclary ET, Wauer R, Phillips B, Brown A, Boer EF, Samani AM, Shapiro MD. An allelic series at the EDNRB2 locus controls diverse piebalding patterns in the domestic pigeon. PLoS Genet 2023; 19:e1010880. [PMID: 37862332 PMCID: PMC10588866 DOI: 10.1371/journal.pgen.1010880] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Accepted: 09/25/2023] [Indexed: 10/22/2023] Open
Abstract
Variation in pigment patterns within and among vertebrate species reflects underlying changes in cell migration and function that can impact health, reproductive success, and survival. The domestic pigeon (Columba livia) is an exceptional model for understanding the genetic changes that give rise to diverse pigment patterns, as selective breeding has given rise to hundreds of breeds with extensive variation in plumage color and pattern. Here, we map the genetic architecture of a suite of pigmentation phenotypes known as piebalding. Piebalding is characterized by patches of pigmented and non-pigmented feathers, and these plumage patterns are often breed-specific and stable across generations. Using a combination of quantitative trait locus mapping in F2 laboratory crosses and genome-wide association analysis, we identify a locus associated with piebalding across many pigeon breeds. This shared locus harbors a candidate gene, EDNRB2, that is a known regulator of pigment cell migration, proliferation, and survival. We discover multiple distinct haplotypes at the EDNRB2 locus in piebald pigeons, which include a mix of protein-coding, noncoding, and structural variants that are associated with depigmentation in specific plumage regions. These results identify a role for EDNRB2 in pigment patterning in the domestic pigeon, and highlight how repeated selection at a single locus can generate a diverse array of stable and heritable pigment patterns.
Collapse
Affiliation(s)
- Emily T. Maclary
- School of Biological Sciences, University of Utah, Salt Lake City, Utah, United States of America
| | - Ryan Wauer
- School of Biological Sciences, University of Utah, Salt Lake City, Utah, United States of America
| | - Bridget Phillips
- School of Biological Sciences, University of Utah, Salt Lake City, Utah, United States of America
| | - Audrey Brown
- School of Biological Sciences, University of Utah, Salt Lake City, Utah, United States of America
| | - Elena F. Boer
- School of Biological Sciences, University of Utah, Salt Lake City, Utah, United States of America
| | - Atoosa M. Samani
- School of Biological Sciences, University of Utah, Salt Lake City, Utah, United States of America
| | - Michael D. Shapiro
- School of Biological Sciences, University of Utah, Salt Lake City, Utah, United States of America
| |
Collapse
|
|
3
|
Maclary ET, Wauer R, Phillips B, Brown A, Boer EF, Samani AM, Shapiro MD. An allelic series at the EDNRB2 locus controls diverse piebalding patterns in the domestic pigeon. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.07.26.550625. [PMID: 37546953 PMCID: PMC10402103 DOI: 10.1101/2023.07.26.550625] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/08/2023]
Abstract
Variation in pigment patterns within and among vertebrate species reflects underlying changes in cell migration and function that can impact health, reproductive success, and survival. The domestic pigeon (Columba livia) is an exceptional model for understanding the genetic changes that give rise to diverse pigment patterns, as selective breeding has given rise to hundreds of breeds with extensive variation in plumage color and pattern. Here, we map the genetic architecture of a suite of pigmentation phenotypes known as piebalding. Piebalding is characterized by patches of pigmented and non-pigmented feathers, and these plumage patterns are often breed-specific and stable across generations. Using a combination of quantitative trait locus mapping in F2 laboratory crosses and genome-wide association analysis, we identify a locus associated with piebalding across many pigeon breeds. This shared locus harbors a candidate gene, EDNRB2, that is a known regulator of pigment cell migration, proliferation, and survival. We discover multiple distinct haplotypes at the EDNRB2 locus in piebald pigeons, which include a mix of protein-coding, noncoding, and structural variants that are associated with depigmentation in specific plumage regions. These results identify a role for EDNRB2 in pigment patterning in the domestic pigeon, and highlight how repeated selection at a single locus can generate a diverse array of stable and heritable pigment patterns.
Collapse
Affiliation(s)
- Emily T. Maclary
- School of Biological Sciences, University of Utah, Salt Lake City, UT 84112, USA
| | - Ryan Wauer
- School of Biological Sciences, University of Utah, Salt Lake City, UT 84112, USA
| | - Bridget Phillips
- School of Biological Sciences, University of Utah, Salt Lake City, UT 84112, USA
| | - Audrey Brown
- School of Biological Sciences, University of Utah, Salt Lake City, UT 84112, USA
| | - Elena F. Boer
- School of Biological Sciences, University of Utah, Salt Lake City, UT 84112, USA
| | - Atoosa M. Samani
- School of Biological Sciences, University of Utah, Salt Lake City, UT 84112, USA
| | - Michael D. Shapiro
- School of Biological Sciences, University of Utah, Salt Lake City, UT 84112, USA
| |
Collapse
|
|
4
|
Fernandes B, Cavaco-Paulo A, Matamá T. A Comprehensive Review of Mammalian Pigmentation: Paving the Way for Innovative Hair Colour-Changing Cosmetics. BIOLOGY 2023; 12:biology12020290. [PMID: 36829566 PMCID: PMC9953601 DOI: 10.3390/biology12020290] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Revised: 01/26/2023] [Accepted: 02/09/2023] [Indexed: 02/15/2023]
Abstract
The natural colour of hair shafts is formed at the bulb of hair follicles, and it is coupled to the hair growth cycle. Three critical processes must happen for efficient pigmentation: (1) melanosome biogenesis in neural crest-derived melanocytes, (2) the biochemical synthesis of melanins (melanogenesis) inside melanosomes, and (3) the transfer of melanin granules to surrounding pre-cortical keratinocytes for their incorporation into nascent hair fibres. All these steps are under complex genetic control. The array of natural hair colour shades are ascribed to polymorphisms in several pigmentary genes. A myriad of factors acting via autocrine, paracrine, and endocrine mechanisms also contributes for hair colour diversity. Given the enormous social and cosmetic importance attributed to hair colour, hair dyeing is today a common practice. Nonetheless, the adverse effects of the long-term usage of such cosmetic procedures demand the development of new methods for colour change. In this context, case reports of hair lightening, darkening and repigmentation as a side-effect of the therapeutic usage of many drugs substantiate the possibility to tune hair colour by interfering with the biology of follicular pigmentary units. By scrutinizing mammalian pigmentation, this review pinpoints key targetable processes for the development of innovative cosmetics that can safely change the hair colour from the inside out.
Collapse
Affiliation(s)
- Bruno Fernandes
- CEB—Centre of Biological Engineering, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal
| | - Artur Cavaco-Paulo
- CEB—Centre of Biological Engineering, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal
- LABBELS—Associate Laboratory, 4710-057 Braga, Portugal
- Correspondence: (A.C.-P.); (T.M.); Tel.: +351-253-604-409 (A.C.-P.); +351-253-601-599 (T.M.)
| | - Teresa Matamá
- CEB—Centre of Biological Engineering, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal
- LABBELS—Associate Laboratory, 4710-057 Braga, Portugal
- Correspondence: (A.C.-P.); (T.M.); Tel.: +351-253-604-409 (A.C.-P.); +351-253-601-599 (T.M.)
| |
Collapse
|
|
5
|
Zhang P, Cao Y, Fu Y, Zhu H, Xu S, Zhang Y, Li W, Sun G, Jiang R, Han R, Li H, Li G, Tian Y, Liu X, Kang X, Li D. Revealing the Regulatory Mechanism of lncRNA-LMEP on Melanin Deposition Based on High-Throughput Sequencing in Xichuan Chicken Skin. Genes (Basel) 2022; 13:2143. [PMID: 36421818 PMCID: PMC9690664 DOI: 10.3390/genes13112143] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2022] [Revised: 11/09/2022] [Accepted: 11/12/2022] [Indexed: 08/27/2023] Open
Abstract
The therapeutic, medicinal, and nourishing properties of black-bone chickens are highly regarded by consumers in China. However, some birds may have yellow skin (YS) or light skin rather than black skin (BS), which causes economic losses every year. Long noncoding RNAs (lncRNAs) are widely present in living organisms, and they perform various biological functions. Many genes associated with BS pigmentation have been discovered, but the lncRNAs involved and their detailed mechanisms have remained untested. We detected 56 differentially expressed lncRNAs from the RNA-seq of dorsal skin (BS versus YS) and found that TCONS_00054154 plays a vital role in melanogenesis by the combined analysis of lncRNAs and mRNAs. We found that the full length of the TCONS_00054154 sequence was 3093 bp by RACE PCR, and we named it LMEP. Moreover, a subcellular localization analysis identified that LMEP is mainly present in the cytoplasm. After the overexpression and the interference with LMEP, the tyrosinase content significantly increased and decreased, respectively (p < 0.05). In summary, we identified the important lncRNAs of chicken skin pigmentation and initially determined the effect of LMEP on melanin deposition.
Collapse
Affiliation(s)
- Pengwei Zhang
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou 450046, China
| | - Yanfang Cao
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou 450046, China
| | - Yawei Fu
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou 450046, China
| | - Huiyuan Zhu
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou 450046, China
| | - Shuohui Xu
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou 450046, China
| | - Yanhua Zhang
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou 450046, China
- Henan Innovative Engineering Research Center of Poultry Germplasm Resource, Zhengzhou 450046, China
| | - Wenting Li
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou 450046, China
- Henan Innovative Engineering Research Center of Poultry Germplasm Resource, Zhengzhou 450046, China
| | - Guirong Sun
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou 450046, China
- Henan Innovative Engineering Research Center of Poultry Germplasm Resource, Zhengzhou 450046, China
| | - Ruirui Jiang
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou 450046, China
- Henan Innovative Engineering Research Center of Poultry Germplasm Resource, Zhengzhou 450046, China
| | - Ruili Han
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou 450046, China
- Henan Innovative Engineering Research Center of Poultry Germplasm Resource, Zhengzhou 450046, China
| | - Hong Li
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou 450046, China
- Henan Innovative Engineering Research Center of Poultry Germplasm Resource, Zhengzhou 450046, China
| | - Guoxi Li
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou 450046, China
- Henan Innovative Engineering Research Center of Poultry Germplasm Resource, Zhengzhou 450046, China
| | - Yadong Tian
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou 450046, China
- Henan Innovative Engineering Research Center of Poultry Germplasm Resource, Zhengzhou 450046, China
| | - Xiaojun Liu
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou 450046, China
- Henan Innovative Engineering Research Center of Poultry Germplasm Resource, Zhengzhou 450046, China
| | - Xiangtao Kang
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou 450046, China
- Henan Innovative Engineering Research Center of Poultry Germplasm Resource, Zhengzhou 450046, China
| | - Donghua Li
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou 450046, China
- Henan Innovative Engineering Research Center of Poultry Germplasm Resource, Zhengzhou 450046, China
| |
Collapse
|
|
6
|
Kelsh RN, Camargo Sosa K, Farjami S, Makeev V, Dawes JHP, Rocco A. Cyclical fate restriction: a new view of neural crest cell fate specification. Development 2021; 148:273451. [PMID: 35020872 DOI: 10.1242/dev.176057] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Neural crest cells are crucial in development, not least because of their remarkable multipotency. Early findings stimulated two hypotheses for how fate specification and commitment from fully multipotent neural crest cells might occur, progressive fate restriction (PFR) and direct fate restriction, differing in whether partially restricted intermediates were involved. Initially hotly debated, they remain unreconciled, although PFR has become favoured. However, testing of a PFR hypothesis of zebrafish pigment cell development refutes this view. We propose a novel 'cyclical fate restriction' hypothesis, based upon a more dynamic view of transcriptional states, reconciling the experimental evidence underpinning the traditional hypotheses.
Collapse
Affiliation(s)
- Robert N Kelsh
- Department of Biology & Biochemistry, University of Bath, Bath, BA2 7AY, UK
| | - Karen Camargo Sosa
- Department of Biology & Biochemistry, University of Bath, Bath, BA2 7AY, UK
| | - Saeed Farjami
- Department of Microbial Sciences, FHMS, University of Surrey, Guildford, GU2 7XH, UK
| | - Vsevolod Makeev
- Department of Computational Systems Biology, Vavilov Institute of General Genetics, Russian Academy of Sciences, Ul. Gubkina 3, Moscow, 119991, Russian Federation.,Department of Biological and Medical Physics, Moscow Institute of Physics and Technology, Dolgoprudny, Moscow Region, 141701, Russian Federation
| | - Jonathan H P Dawes
- Department of Mathematical Sciences, University of Bath, Bath, BA2 7AY, UK
| | - Andrea Rocco
- Department of Microbial Sciences, FHMS, University of Surrey, Guildford, GU2 7XH, UK.,Department of Physics, FEPS, University of Surrey, Guildford, GU2 7XH, UK
| |
Collapse
|
|
7
|
Zhang X, Wang H, Lou L, Li Q, Zhang L, Ge Y. Transcript expression profiling of fibromelanosis-related genes in black-bone chickens. Br Poult Sci 2021; 63:133-141. [PMID: 34402346 DOI: 10.1080/00071668.2021.1966750] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
1. The aim of the present study was to identify differentially expressed genes (DEGs) and metabolic pathways involved in this phenotype. Fibromelanosis is the most striking feature of black-bone chickens, such as the Silkie and Dongxiang indigenous breeds. Due to the accumulation of eumelanin in connective tissues, fibromelanosis manifests as black colouration of the skin, muscles, gut, and periosteum. Studies on fibromelanosis can provide useful information pertaining to human diseases and offer commercial value to the poultry industry. However, the genetic basis of fibromelanosis remains unclear.2. Digital gene expression analysis was performed on black and white skin samples collected from the HW1 black-bone chicken line to detect differences in genome-wide expression patterns. A total of >30 billion bp were sequenced, and 2,707,926,466 bp and 2,948,782,964 bp of clean data obtained for creation of libraries for black and white skin, respectively. In total, 252 DEGs from 15,508 mapped genes were identified with 83 up-regulated in white skin and 169 up-regulated in black skin.3. Gene ontology analysis highlighted that genes from the extracellular region and associated components were abundant among the DEGs. Pathway analysis revealed that many DEGs were linked to amino acid metabolism and the immune system. qRT-PCR validation using 14 genes showed good conformity with the sequence analysis of fibromelanosis-related genes.4. The results showed that L-dopachrometautomerase precursor (DCT), tyrosine aminotransferase (TAT), 4-hydroxyphenylpyruvate dioxygenase (HPD) from the tyrosine metabolism pathway, coagulation factor II (F2), fibrinogen beta chain (FGB), plasminogen (PLG) and complement component 7 (C7) from the complement and coagulation cascades were important genes in the fibromelanosis process in black-bone chickens. These candidate genes require further correlation analysis and functional verification.
Collapse
Affiliation(s)
- X Zhang
- Institute of Animal Husbandry, Hangzhou Academy of Agricultural Sciences, Hangzhou, China
| | - H Wang
- Institute of Animal Husbandry, Hangzhou Academy of Agricultural Sciences, Hangzhou, China
| | - L Lou
- Institute of Animal Husbandry, Hangzhou Academy of Agricultural Sciences, Hangzhou, China
| | - Q Li
- Institute of Animal Husbandry, Hangzhou Academy of Agricultural Sciences, Hangzhou, China
| | - L Zhang
- Institute of Animal Husbandry, Hangzhou Academy of Agricultural Sciences, Hangzhou, China
| | - Y Ge
- Institute of Animal Husbandry, Hangzhou Academy of Agricultural Sciences, Hangzhou, China
| |
Collapse
|
|
8
|
Farina AR, Cappabianca LA, Zelli V, Sebastiano M, Mackay AR. Mechanisms involved in selecting and maintaining neuroblastoma cancer stem cell populations, and perspectives for therapeutic targeting. World J Stem Cells 2021; 13:685-736. [PMID: 34367474 PMCID: PMC8316860 DOI: 10.4252/wjsc.v13.i7.685] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 03/09/2021] [Accepted: 04/14/2021] [Indexed: 02/06/2023] Open
Abstract
Pediatric neuroblastomas (NBs) are heterogeneous, aggressive, therapy-resistant embryonal tumours that originate from cells of neural crest (NC) origin and in particular neuroblasts committed to the sympathoadrenal progenitor cell lineage. Therapeutic resistance, post-therapeutic relapse and subsequent metastatic NB progression are driven primarily by cancer stem cell (CSC)-like subpopulations, which through their self-renewing capacity, intermittent and slow cell cycles, drug-resistant and reversibly adaptive plastic phenotypes, represent the most important obstacle to improving therapeutic outcomes in unfavourable NBs. In this review, dedicated to NB CSCs and the prospects for their therapeutic eradication, we initiate with brief descriptions of the unique transient vertebrate embryonic NC structure and salient molecular protagonists involved NC induction, specification, epithelial to mesenchymal transition and migratory behaviour, in order to familiarise the reader with the embryonic cellular and molecular origins and background to NB. We follow this by introducing NB and the potential NC-derived stem/progenitor cell origins of NBs, before providing a comprehensive review of the salient molecules, signalling pathways, mechanisms, tumour microenvironmental and therapeutic conditions involved in promoting, selecting and maintaining NB CSC subpopulations, and that underpin their therapy-resistant, self-renewing metastatic behaviour. Finally, we review potential therapeutic strategies and future prospects for targeting and eradication of these bastions of NB therapeutic resistance, post-therapeutic relapse and metastatic progression.
Collapse
Affiliation(s)
- Antonietta Rosella Farina
- Department of Applied Clinical and Biotechnological Sciences, University of L'Aquila, L'Aquila 67100, AQ, Italy
| | - Lucia Annamaria Cappabianca
- Department of Applied Clinical and Biotechnological Sciences, University of L'Aquila, L'Aquila 67100, AQ, Italy
| | - Veronica Zelli
- Department of Applied Clinical and Biotechnological Sciences, University of L'Aquila, L'Aquila 67100, AQ, Italy
| | - Michela Sebastiano
- Department of Applied Clinical and Biotechnological Sciences, University of L'Aquila, L'Aquila 67100, AQ, Italy
| | - Andrew Reay Mackay
- Department of Applied Clinical and Biotechnological Sciences, University of L'Aquila, L'Aquila 67100, AQ, Italy.
| |
Collapse
|
|
9
|
Bovo S, Schiavo G, Kazemi H, Moscatelli G, Ribani A, Ballan M, Bonacini M, Prandi M, Dall'Olio S, Fontanesi L. Exploiting within-breed variability in the autochthonous Reggiana breed identified several candidate genes affecting pigmentation-related traits, stature and udder defects in cattle. Anim Genet 2021; 52:579-597. [PMID: 34182594 PMCID: PMC8519023 DOI: 10.1111/age.13109] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/11/2021] [Indexed: 01/13/2023]
Abstract
Autochthonous cattle breeds constitute important reservoirs of genetic diversity. Reggiana is an Italian local cattle breed reared in the north of Italy for the production of a mono‐breed Parmigiano–Reggiano cheese. Reggiana cattle usually have a classical solid red coat colour and pale muzzle. As part of the strategies designed for the sustainable conservation of this genetic resource, we investigated at the genome‐wise level the within‐breed detected variability of three pigmentation‐related traits (intensity of red coat colour, based on three classes – light/diluted, normal and dark; spotted patterns/piebaldism that sometime emerge in the breed; muzzle colour – pink/pale, grey and black), stature, presence/absence and number of supernumerary teats and teat length. A total of 1776 Reggiana cattle (about two‐thirds of the extant breed population) were genotyped with the GeneSeek GGP Bovine 150k SNP array and single‐marker and haplotype‐based GWASs were carried out. The results indicated that two main groups of genetic factors affect the intensity of red coat colour: darkening genes (including EDN3 and a few other genes) and diluting genes (including PMEL and a few other genes). Muzzle colour was mainly determined by MC1R gene markers. Piebaldism was mainly associated with KIT gene markers. Stature was associated with BTA6 markers upstream of the NCAPG–LCORL genes. Teat defects were associated with TBX3/TBX5, MCC and LGR5 genes. Overall, the identified genomic regions not only can be directly used in selection plans in the Reggiana breed, but also contribute to clarifying the genetic mechanisms involved in determining exterior traits in cattle.
Collapse
Affiliation(s)
- S Bovo
- Division of Animal Sciences, Department of Agricultural and Food Science, University of Bologna, Viale Giuseppe Fanin 46, Bologna, 40127, Italy
| | - G Schiavo
- Division of Animal Sciences, Department of Agricultural and Food Science, University of Bologna, Viale Giuseppe Fanin 46, Bologna, 40127, Italy
| | - H Kazemi
- Division of Animal Sciences, Department of Agricultural and Food Science, University of Bologna, Viale Giuseppe Fanin 46, Bologna, 40127, Italy
| | - G Moscatelli
- Division of Animal Sciences, Department of Agricultural and Food Science, University of Bologna, Viale Giuseppe Fanin 46, Bologna, 40127, Italy
| | - A Ribani
- Division of Animal Sciences, Department of Agricultural and Food Science, University of Bologna, Viale Giuseppe Fanin 46, Bologna, 40127, Italy
| | - M Ballan
- Division of Animal Sciences, Department of Agricultural and Food Science, University of Bologna, Viale Giuseppe Fanin 46, Bologna, 40127, Italy
| | - M Bonacini
- Associazione Nazionale Allevatori Bovini di Razza Reggiana (ANABORARE), Via Masaccio 11, Reggio Emilia, 42124, Italy
| | - M Prandi
- Associazione Nazionale Allevatori Bovini di Razza Reggiana (ANABORARE), Via Masaccio 11, Reggio Emilia, 42124, Italy
| | - S Dall'Olio
- Division of Animal Sciences, Department of Agricultural and Food Science, University of Bologna, Viale Giuseppe Fanin 46, Bologna, 40127, Italy
| | - L Fontanesi
- Division of Animal Sciences, Department of Agricultural and Food Science, University of Bologna, Viale Giuseppe Fanin 46, Bologna, 40127, Italy
| |
Collapse
|
|
10
|
Kang YN, Fung C, Vanden Berghe P. Gut innervation and enteric nervous system development: a spatial, temporal and molecular tour de force. Development 2021; 148:148/3/dev182543. [PMID: 33558316 DOI: 10.1242/dev.182543] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
During embryonic development, the gut is innervated by intrinsic (enteric) and extrinsic nerves. Focusing on mammalian ENS development, in this Review we highlight how important the different compartments of this innervation are to assure proper gut function. We specifically address the three-dimensional architecture of the innervation, paying special attention to the differences in development along the longitudinal and circumferential axes of the gut. We review recent information about the formation of both intrinsic innervation, which is fairly well-known, as well as the establishment of the extrinsic innervation, which, despite its importance in gut-brain signaling, has received much less attention. We further discuss how external microbial and nutritional cues or neuroimmune interactions may influence development of gut innervation. Finally, we provide summary tables, describing the location and function of several well-known molecules, along with some newer factors that have more recently been implicated in the development of gut innervation.
Collapse
Affiliation(s)
- Yi-Ning Kang
- Laboratory for Enteric NeuroScience (LENS), Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven 3000, Belgium
| | - Candice Fung
- Laboratory for Enteric NeuroScience (LENS), Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven 3000, Belgium
| | - Pieter Vanden Berghe
- Laboratory for Enteric NeuroScience (LENS), Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven 3000, Belgium
| |
Collapse
|
|
11
|
Teixeira BL, Amarante-Silva D, Visoni SB, Garcez RC, Trentin AG. FGF2 Stimulates the Growth and Improves the Melanocytic Commitment of Trunk Neural Crest Cells. Cell Mol Neurobiol 2020; 40:383-393. [PMID: 31555941 PMCID: PMC11448768 DOI: 10.1007/s10571-019-00738-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2019] [Accepted: 09/14/2019] [Indexed: 12/13/2022]
Abstract
Neural crest cells (NCCs) comprise a population of multipotent progenitors and stem cells at the origin of the peripheral nervous system (PNS) and melanocytes of skin, which are profoundly influenced by microenvironmental factors, among which is basic fibroblast growth factor 2 (FGF2). In this work, we further investigated the role of this growth factor in quail trunk NC morphogenesis and demonstrated its huge effect in NCC growth mainly by stimulating cell proliferation but also reducing cell death, despite that NCC migration from the neural tube explant was not affected. Moreover, following FGF2 treatment, reduced expression of the early NC markers Sox10 and FoxD3 and improved proliferation of HNK1-positive NCC were observed. Since these markers are involved in the regulation of glial and melanocytic fate of NC, the effect of FGF2 on NCC differentiation was investigated. Therefore, in the presence of FGF2, increased proportions of NCCs positives to the melanoblast marker Mitf as well as NCCs double stained to Mitf and BrdU were recorded. In addition, treatment with FGF2, followed by differentiation medium, resulted in increased expression of melanin and improved proportion of melanin-pigmented melanocytes without alteration in the glial marker Schwann myelin protein (SMP). Taken together, these data further reveal the important role of FGF2 in NCC proliferation, survival, and differentiation, particularly in melanocyte development. This is the first demonstration of FGF2 effects in melanocyte commitment of NC and in the proliferation of Mitf-positive melanoblasts. Elucidating the differentiation process of embryonic NCCs brings us a step closer to understanding the development of the PNS and then undertaking the search for advanced technologies to prevent, or treat, injuries caused by NC-related disorders, also known as neurocristopathies.
Collapse
Affiliation(s)
- Bianca Luise Teixeira
- Department of Cell Biology, Embryology and Genetics, Federal University of Santa Catarina, Florianopolis-SC, Campus Universitário,Trindade, Florianópolis, SC, 88040-900, Brazil
| | - Diego Amarante-Silva
- Department of Cell Biology, Embryology and Genetics, Federal University of Santa Catarina, Florianopolis-SC, Campus Universitário,Trindade, Florianópolis, SC, 88040-900, Brazil
| | - Silvia Beatriz Visoni
- Department of Cell Biology, Embryology and Genetics, Federal University of Santa Catarina, Florianopolis-SC, Campus Universitário,Trindade, Florianópolis, SC, 88040-900, Brazil
| | - Ricardo Castilho Garcez
- Department of Cell Biology, Embryology and Genetics, Federal University of Santa Catarina, Florianopolis-SC, Campus Universitário,Trindade, Florianópolis, SC, 88040-900, Brazil
| | - Andrea Gonçalves Trentin
- Department of Cell Biology, Embryology and Genetics, Federal University of Santa Catarina, Florianopolis-SC, Campus Universitário,Trindade, Florianópolis, SC, 88040-900, Brazil.
- National Institute of Science and Technology for Regenerative Medicine, Av. Carlos Chagas Filho, n°373, Rio De Janeiro, RJ, CEP: 21941902, Brazil.
| |
Collapse
|
|
12
|
Briyal S, Ranjan AK, Hornick MG, Puppala AK, Luu T, Gulati A. Anti-apoptotic activity of ET B receptor agonist, IRL-1620, protects neural cells in rats with cerebral ischemia. Sci Rep 2019; 9:10439. [PMID: 31320660 PMCID: PMC6639304 DOI: 10.1038/s41598-019-46203-x] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2018] [Accepted: 01/04/2019] [Indexed: 02/08/2023] Open
Abstract
Endothelin-B receptor agonist, IRL-1620, provides significant neuroprotection following cerebral ischemia in rats. Whether this neuroprotection is due to inhibition of apoptosis is unknown. IRL-1620-treated rats following permanent middle cerebral artery occlusion (MCAO) showed significant improvement in neurological and motor functions along with a decrease in infarct volume at 24 h (-81.3%) and day 7 (-73.0%) compared to vehicle group. Cerebral blood flow (CBF) significantly improved in IRL-1620-treated animals compared to vehicle by day 7 post MCAO. IRL-1620-treated rats showed an increase in phospho-Akt and decrease in Bad level 7 h post-occlusion compared to vehicle, while Akt and Bad expression was similar in cerebral hemispheres at 24 h post-MCAO. The phospho-Bad level was lower in vehicle- but not in IRL-1620-treated rats at 24 h. Anti-apoptotic Bcl-2 expression decreased, while pro-apoptotic Bax expression increased in vehicle-treated MCAO rats, these changes were attenuated (P < 0.01) by IRL-1620. Mitochondrial membrane-bound Bax intensity significantly decreased in IRL-1620 compared to vehicle-treated MCAO rats. IRL-1620 treatment reduced (P < 0.001) the number of TUNEL-positive cells compared to vehicle at 24 h and day 7 post MCAO. The results demonstrate that IRL-1620 is neuroprotective and attenuates neural damage following cerebral ischemia in rats by increasing CBF and reducing apoptosis.
Collapse
Affiliation(s)
- Seema Briyal
- Chicago College of Pharmacy, Midwestern University, Downers Grove, IL, 60515, USA
| | - Amaresh K Ranjan
- Chicago College of Pharmacy, Midwestern University, Downers Grove, IL, 60515, USA
| | - Mary G Hornick
- Chicago College of Pharmacy, Midwestern University, Downers Grove, IL, 60515, USA
| | - Anupama K Puppala
- Chicago College of Pharmacy, Midwestern University, Downers Grove, IL, 60515, USA
| | - Thanh Luu
- Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL, 60515, USA
| | - Anil Gulati
- Chicago College of Pharmacy, Midwestern University, Downers Grove, IL, 60515, USA. .,Pharmazz, Inc., Research and Development, Willowbrook, IL, USA.
| |
Collapse
|
|
13
|
Etchevers HC, Dupin E, Le Douarin NM. The diverse neural crest: from embryology to human pathology. Development 2019; 146:146/5/dev169821. [PMID: 30858200 DOI: 10.1242/dev.169821] [Citation(s) in RCA: 69] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2018] [Accepted: 02/07/2019] [Indexed: 01/13/2023]
Abstract
We review here some of the historical highlights in exploratory studies of the vertebrate embryonic structure known as the neural crest. The study of the molecular properties of the cells that it produces, their migratory capacities and plasticity, and the still-growing list of tissues that depend on their presence for form and function, continue to enrich our understanding of congenital malformations, paediatric cancers and evolutionary biology. Developmental biology has been key to our understanding of the neural crest, starting with the early days of experimental embryology and through to today, when increasingly powerful technologies contribute to further insight into this fascinating vertebrate cell population.
Collapse
Affiliation(s)
- Heather C Etchevers
- Aix-Marseille Université, INSERM, MMG, U1251, 27 boulevard Jean Moulin 13005 Marseille, France
| | - Elisabeth Dupin
- Sorbonne Universités, UPMC Paris 06, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, 75012 Paris, France
| | - Nicole M Le Douarin
- Sorbonne Universités, UPMC Paris 06, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, 75012 Paris, France
| |
Collapse
|
|
14
|
Bhattacharya D, Rothstein M, Azambuja AP, Simoes-Costa M. Control of neural crest multipotency by Wnt signaling and the Lin28/ let-7 axis. eLife 2018; 7:40556. [PMID: 30520734 PMCID: PMC6301792 DOI: 10.7554/elife.40556] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2018] [Accepted: 12/04/2018] [Indexed: 12/21/2022] Open
Abstract
A crucial step in cell differentiation is the silencing of developmental programs underlying multipotency. While much is known about how lineage-specific genes are activated to generate distinct cell types, the mechanisms driving suppression of stemness are far less understood. To address this, we examined the regulation of the transcriptional network that maintains progenitor identity in avian neural crest cells. Our results show that a regulatory circuit formed by Wnt, Lin28a and let-7 miRNAs controls the deployment and the subsequent silencing of the multipotency program in a position-dependent manner. Transition from multipotency to differentiation is determined by the topological relationship between the migratory cells and the dorsal neural tube, which acts as a Wnt-producing stem cell niche. Our findings highlight a mechanism that rapidly silences complex regulatory programs, and elucidate how transcriptional networks respond to positional information during cell differentiation.
Collapse
Affiliation(s)
| | - Megan Rothstein
- Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States
| | - Ana Paula Azambuja
- Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States
| | - Marcos Simoes-Costa
- Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States
| |
Collapse
|
|
15
|
Le Douarin NM, Dupin E. The “beginnings” of the neural crest. Dev Biol 2018; 444 Suppl 1:S3-S13. [DOI: 10.1016/j.ydbio.2018.07.019] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2018] [Revised: 07/20/2018] [Accepted: 07/20/2018] [Indexed: 12/14/2022]
|
|
16
|
Dupin E, Calloni GW, Coelho-Aguiar JM, Le Douarin NM. The issue of the multipotency of the neural crest cells. Dev Biol 2018; 444 Suppl 1:S47-S59. [DOI: 10.1016/j.ydbio.2018.03.024] [Citation(s) in RCA: 67] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2017] [Revised: 03/29/2018] [Accepted: 03/30/2018] [Indexed: 12/25/2022]
|
|
17
|
Bondurand N, Dufour S, Pingault V. News from the endothelin-3/EDNRB signaling pathway: Role during enteric nervous system development and involvement in neural crest-associated disorders. Dev Biol 2018; 444 Suppl 1:S156-S169. [PMID: 30171849 DOI: 10.1016/j.ydbio.2018.08.014] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2018] [Revised: 08/27/2018] [Accepted: 08/27/2018] [Indexed: 01/08/2023]
Abstract
The endothelin system is a vertebrate-specific innovation with important roles in regulating the cardiovascular system and renal and pulmonary processes, as well as the development of the vertebrate-specific neural crest cell population and its derivatives. This system is comprised of three structurally similar 21-amino acid peptides that bind and activate two G-protein coupled receptors. In 1994, knockouts of the Edn3 and Ednrb genes revealed their crucial function during development of the enteric nervous system and melanocytes, two neural-crest derivatives. Since then, human and mouse genetics, combined with cellular and developmental studies, have helped to unravel the role of this signaling pathway during development and adulthood. In this review, we will summarize the known functions of the EDN3/EDNRB pathway during neural crest development, with a specific focus on recent scientific advances, and the enteric nervous system in normal and pathological conditions.
Collapse
Affiliation(s)
- Nadege Bondurand
- Laboratory of Embryology and Genetics of Congenital Malformations, INSERM U1163, Institut Imagine, Paris, France; Paris Descartes-Sorbonne Paris Cité University, Institut Imagine, Paris, France.
| | - Sylvie Dufour
- INSERM, U955, Equipe 06, Créteil 94000, France; Université Paris Est, Faculté de Médecine, Créteil 94000, France
| | - Veronique Pingault
- Laboratory of Embryology and Genetics of Congenital Malformations, INSERM U1163, Institut Imagine, Paris, France; Paris Descartes-Sorbonne Paris Cité University, Institut Imagine, Paris, France; Service de Génétique Moléculaire, Hôpital Necker-Enfants Malades, Assistance Publique - Hôpitaux de Paris, Paris, France
| |
Collapse
|
|
18
|
Münst S, Koch P, Kesavan J, Alexander-Mays M, Münst B, Blaess S, Brüstle O. In vitro segregation and isolation of human pluripotent stem cell-derived neural crest cells. Methods 2017; 133:65-80. [PMID: 29037816 DOI: 10.1016/j.ymeth.2017.09.012] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2017] [Revised: 09/24/2017] [Accepted: 09/27/2017] [Indexed: 01/17/2023] Open
Abstract
The neural crest (NC) is a transient embryonic cell population with remarkable characteristics. After delaminating from the neural tube, NC cells (NCCs) migrate extensively, populate nearly every tissue of the body and differentiate into highly diverse cell types such as peripheral neurons and glia, but also mesenchymal cells including chondrocytes, osteocytes, and adipocytes. While the NC has been extensively studied in several animal models, little is known about human NC development. A number of methods have been established to derive NCCs in vitro from human pluripotent stem cells (hPSC). Typically, these protocols comprise several cell culture steps to enrich for NCCs in the neural derivatives of the differentiating hPSCs. Here we report on a remarkable and hitherto unnoticed in vitro segregation phenomenon that enables direct extraction of virtually pure NCCs during the earliest stages of hPSC differentiation. Upon aggregation to embryoid bodies (EB) and replating, differentiating hPSCs give rise to a population of NCCs, which spontaneously segregate from the EB outgrowth to form conspicuous, macroscopically visible atoll-shaped clusters in the periphery of the EB outgrowth. Isolation of these NC clusters yields p75NTR(+)/SOXE(+) NCCs, which differentiate to peripheral neurons and glia as well as mesenchymal derivatives. Our data indicate that differentiating hPSC cultures recapitulate, in a simplified manner, the physical segregation of central nervous system (CNS) tissue and NCCs. This phenomenon may be exploited for NCC purification and for studying segregation and differentiation processes observed during early human NC development in vitro.
Collapse
Affiliation(s)
- Sabine Münst
- Institute of Reconstructive Neurobiology, Life & Brain Center, University of Bonn Medical Faculty, 53127 Bonn, Germany
| | - Philipp Koch
- Institute of Reconstructive Neurobiology, Life & Brain Center, University of Bonn Medical Faculty, 53127 Bonn, Germany
| | - Jaideep Kesavan
- Institute of Reconstructive Neurobiology, Life & Brain Center, University of Bonn Medical Faculty, 53127 Bonn, Germany
| | - Michael Alexander-Mays
- Institute of Human Genetics, Life & Brain Center, University of Bonn Medical Faculty, 53127 Bonn, Germany
| | - Bernhard Münst
- Institute of Reconstructive Neurobiology, Life & Brain Center, University of Bonn Medical Faculty, 53127 Bonn, Germany
| | - Sandra Blaess
- Institute of Reconstructive Neurobiology, Life & Brain Center, University of Bonn Medical Faculty, 53127 Bonn, Germany
| | - Oliver Brüstle
- Institute of Reconstructive Neurobiology, Life & Brain Center, University of Bonn Medical Faculty, 53127 Bonn, Germany.
| |
Collapse
|
|
19
|
Urtatiz O, Van Raamsdonk CD. Gnaq and Gna11 in the Endothelin Signaling Pathway and Melanoma. Front Genet 2016; 7:59. [PMID: 27148356 PMCID: PMC4837292 DOI: 10.3389/fgene.2016.00059] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2016] [Accepted: 04/01/2016] [Indexed: 12/21/2022] Open
Abstract
In this article, we first briefly outline the function of G protein coupled receptors in cancer, and then specifically examine the roles of the seven transmembrane G protein coupled Endothelin B receptor (Ednrb) and the G proteins, GNAQ and GNA11, in both melanocyte development and melanoma. Ednrb plays an essential role in melanocyte development. GNAQ and GNA11 are oncogenes when mutated in certain types of melanocytic lesions, being extremely frequent in uveal melanoma, which forms from melanocytes located in the eye. Previously, we reported that in mice, Schwann cell precursor derived melanocytes colonize the dermis and hair follicles, while the inter-follicular epidermis is populated by other melanocytes. A pattern has emerged whereby melanocytes whose activities are affected by gain-of-function mutations of the Endothelin 3 ligand and Gαq/11 are the same subset that arise from Schwann cell precursors. Furthermore, the forced expression of the constitutively active human GNAQQ209L oncogene in mouse melanocytes only causes hyper-proliferation in the subset that arise from Schwann cell precursors. This has led us to hypothesize that in Schwann cell precursor derived melanocytes, Ednrb signals through Gαq/11. Ednrb is promiscuous and may signal through other G protein alpha subunits in melanomas located in the inter-follicular epidermis.
Collapse
Affiliation(s)
- Oscar Urtatiz
- Department of Medical Genetics, University of British Columbia Vancouver, BC, Canada
| | | |
Collapse
|
|
20
|
Le Douarin NM, Dupin E. The Pluripotency of Neural Crest Cells and Their Role in Brain Development. Curr Top Dev Biol 2016; 116:659-78. [PMID: 26970647 DOI: 10.1016/bs.ctdb.2015.10.008] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The neural crest (NC) is, in the Chordate phylum, an innovation of vertebrates, which exhibits several original characteristics: its component cells are pluripotent and give rise to both ectodermal and mesodermal cell types. Moreover, during the early stages of neurogenesis, the NC cells exert a paracrine stimulating effect on the development of the preotic brain.
Collapse
Affiliation(s)
- Nicole M Le Douarin
- Collège de France, 3 rue d'Ulm, Paris, France; INSERM U968, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR S 968, Institut de la Vision, Paris, France; CNRS, UMR 7210, Paris, France.
| | - Elisabeth Dupin
- INSERM U968, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR S 968, Institut de la Vision, Paris, France; CNRS, UMR 7210, Paris, France
| |
Collapse
|
|
21
|
Shakhova O, Sommer L. In Vitro Derivation of Melanocytes from Embryonic Neural Crest Stem Cells. Methods Mol Biol 2015. [PMID: 26659800 DOI: 10.1007/7651_2015_305] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/05/2023]
Abstract
During development, melanocyte progenitors originate from the neural crest, a transient embryonic structure in vertebrates that gives rise to a variety of cell types including neurons and glia of the peripheral nervous system, smooth muscle cells of the cardiovascular system, chondrocytes and osteoblasts of the craniofacial elements, and pigment cells in the skin. In this chapter, we describe a method for the differentiation of multipotent embryonic neural crest stem cells into differentiated pigmented melanocytes by using in vitro explant culture system. This protocol allows the dissection of genetic and cellular mechanisms regulating neural crest stem cell and melanocyte development. Based on this knowledge it is possible to make predictions about processes that might also be implicated in melanoma initiation and progression.
Collapse
Affiliation(s)
- Olga Shakhova
- Department of Oncology, University Hospital Zurich, Wagistrasse 14, 8952, Schlieren, Switzerland.
- Institute of Anatomy, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland.
| | - Lukas Sommer
- Institute of Anatomy, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland
| |
Collapse
|
|
22
|
Motohashi T, Kunisada T. Extended multipotency of neural crest cells and neural crest-derived cells. Curr Top Dev Biol 2015; 111:69-95. [PMID: 25662258 DOI: 10.1016/bs.ctdb.2014.11.003] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Neural crest cells (NCC) are migratory multipotent cells that give rise to diverse derivatives. They generate various cell types during embryonic development, including neurons and glial cells of the peripheral sensory and autonomic ganglia, Schwann cells, melanocytes, endocrine cells, smooth muscle, and skeletal and connective tissue cells of the craniofacial complex. The multipotency of NCC is thought to be transient at the early stage of NCC generation; once NCC emerge from the neural tube, they change into lineage-restricted precursors. Although many studies have described the clear segregation of NCC lineages right after their delamination from the neural tube, recent reports suggest that multipotent neural crest stem cells (NCSC) are present not only in migrating NCC in the embryo, but also in their target tissues in the fetus and adult. Furthermore, fully differentiated NCC-derived cells such as glial cells and melanocytes have been shown to dedifferentiate or transdifferentiate into other NCC derivatives. The multipotency of migratory and postmigratory NCC-derived cells was found to be similar to that of NCSC. Collectively, these findings support the multipotency or plasticity of NCC and NCC-derived cells.
Collapse
Affiliation(s)
- Tsutomu Motohashi
- Department of Tissue and Organ Development, Regeneration and Advanced Medical Science, Gifu University Graduate School of Medicine, Gifu, Japan; Japan Science and Technology Agency (JST), Core Research for Evolutional Science and Technology (CREST), Tokyo, Japan.
| | - Takahiro Kunisada
- Department of Tissue and Organ Development, Regeneration and Advanced Medical Science, Gifu University Graduate School of Medicine, Gifu, Japan; Japan Science and Technology Agency (JST), Core Research for Evolutional Science and Technology (CREST), Tokyo, Japan
| |
Collapse
|
|
23
|
Dupin E, Le Douarin NM. The neural crest, a multifaceted structure of the vertebrates. ACTA ACUST UNITED AC 2014; 102:187-209. [PMID: 25219958 DOI: 10.1002/bdrc.21080] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2014] [Accepted: 08/22/2014] [Indexed: 12/29/2022]
Abstract
In this review, several features of the cells originating from the lateral borders of the primitive neural anlagen, the neural crest (NC) are considered. Among them, their multipotentiality, which together with their migratory properties, leads them to colonize the developing body and to participate in the development of many tissues and organs. The in vitro analysis of the developmental capacities of single NC cells (NCC) showed that they present several analogies with the hematopoietic cells whose differentiation involves the activity of stem cells endowed with different arrays of developmental potentialities. The permanence of such NC stem cells in the adult organism raises the problem of their role at that stage of life. The NC has appeared during evolution in the vertebrate phylum and is absent in their Protocordates ancestors. The major role of the NCC in the development of the vertebrate head points to a critical role for this structure in the remarkable diversification and radiation of this group of animals.
Collapse
Affiliation(s)
- Elisabeth Dupin
- INSERM, U968, Paris, F-75012, France; Sorbonne Universités, UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, F-75012, France; CNRS, UMR_7210, Paris, F-75012, France
| | | |
Collapse
|
|
24
|
Kunisada T, Tezulka KI, Aoki H, Motohashi T. The stemness of neural crest cells and their derivatives. ACTA ACUST UNITED AC 2014; 102:251-62. [DOI: 10.1002/bdrc.21079] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2014] [Accepted: 08/22/2014] [Indexed: 01/22/2023]
Affiliation(s)
- Takahiro Kunisada
- Department of Tissue and Organ Development, Regeneration, and Advanced Medical Science; Gifu University Graduate School of Medicine, 1-1, Yanagido; Gifu 501-1194 Japan
| | - Ken-Ichi Tezulka
- Department of Tissue and Organ Development, Regeneration, and Advanced Medical Science; Gifu University Graduate School of Medicine, 1-1, Yanagido; Gifu 501-1194 Japan
| | - Hitomi Aoki
- Department of Tissue and Organ Development, Regeneration, and Advanced Medical Science; Gifu University Graduate School of Medicine, 1-1, Yanagido; Gifu 501-1194 Japan
| | - Tsutomu Motohashi
- Department of Tissue and Organ Development, Regeneration, and Advanced Medical Science; Gifu University Graduate School of Medicine, 1-1, Yanagido; Gifu 501-1194 Japan
| |
Collapse
|
|
25
|
Developmental pathways activated in melanocytes and melanoma. Arch Biochem Biophys 2014; 563:13-21. [PMID: 25109840 DOI: 10.1016/j.abb.2014.07.023] [Citation(s) in RCA: 66] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2014] [Revised: 07/14/2014] [Accepted: 07/17/2014] [Indexed: 12/25/2022]
Abstract
Cutaneous malignant melanomas originate primarily within epidermal melanocytic cells. Melanoma cells share many characteristics with melanocyte precursors, suggesting that melanoma cells utilize the developmental programs of their normal counterpart for their own progression. The pigmentation system provides an advantageous model to assess survival pathway interactions in the melanocytic lineage, as genetic alterations controlling melanocyte development can be easily detectable by coat color phenotype that do not affect the viability of an animal. By integrating combinatorial gene knockout approaches, cell-based assays and immunohistochemical observations, recent studies have illustrated several genes and pathways that play important roles both in melanocyte specification and maintenance and in melanoma formation and progression. We are reviewing those genes and pathways to understand the connection between normal and cancerous development and to reveal therapeutic potential of targeting developmental pathways for melanoma therapy.
Collapse
|
|
26
|
Kinoshita K, Akiyama T, Mizutani M, Shinomiya A, Ishikawa A, Younis HH, Tsudzuki M, Namikawa T, Matsuda Y. Endothelin receptor B2 (EDNRB2) is responsible for the tyrosinase-independent recessive white (mo(w) ) and mottled (mo) plumage phenotypes in the chicken. PLoS One 2014; 9:e86361. [PMID: 24466053 PMCID: PMC3900529 DOI: 10.1371/journal.pone.0086361] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2013] [Accepted: 12/08/2013] [Indexed: 12/03/2022] Open
Abstract
A mutation that confers white plumage with black eyes was identified in the Minohiki breed of Japanese native chicken (Gallus gallus domesticus). The white plumage, with a few partially pigmented feathers, was not associated with the tyrosinase gene, and displayed an autosomal recessive mode of inheritance against the pigmented phenotype. All F1 offspring derived from crosses with mottled chickens (mo/mo), which show characteristic pigmented feathers with white tips, had plumage with a mottled-like pattern. This result indicates that the white plumage mutation is a novel allele at the mo locus; we propose the gene symbol mo(w) for this mutant allele. Furthermore, the F1 hybrid between the mo(w) /mo(w) chicken and the panda (s/s) mutant of Japanese quail (Coturnix japonica), whose causative gene is the endothelin receptor B2 (EDNRB2) gene, showed a mo(w)/mo(w) chicken-like plumage, suggesting the possibility that the mutations in parental species are alleles of the same gene, EDNRB2. Nucleotide sequencing of the entire coding region of EDNRB2 revealed a non-synonymous G1008T substitution, which causes Cys244Phe amino acid substitution in exon 5 (which is part of the extracellular loop between the putative fourth and fifth transmembrane domains of EDNRB2) in the mutant chicken. This Cys244Phe mutation was also present in individuals of four Japanese breeds with white plumage. We also identified a non-synonymous substitution leading to Arg332His substitution that was responsible for the mottled (mo/mo) plumage phenotype. These results suggest that the EDN3 (endothelin 3)-EDNRB2 signaling is essential for normal pigmentation in birds, and that the mutations of EDNRB2 may cause defective binding of the protein with endothelins, which interferes with melanocyte differentiation, proliferation, and migration.
Collapse
Affiliation(s)
- Keiji Kinoshita
- Avian Bioscience Research Center, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan
| | | | - Makoto Mizutani
- Avian Bioscience Research Center, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan
| | - Ai Shinomiya
- Department of Biology, Keio University, Yokohama, Japan
| | - Akira Ishikawa
- Laboratory of Animal Genetics, Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan
| | - Hassan Hassan Younis
- Laboratory of Animal Genetics, Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan
- Department of Poultry Production, Faculty of Agriculture, Kafr El-Sheikh University, Kafr El-Sheikh, Egypt
| | - Masaoki Tsudzuki
- Laboratory of Animal Breeding and Genetics, Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima, Japan
- Japanese Avian Bioresource Project Research Center, Hiroshima University, Higashi-Hiroshima, Japan
| | - Takao Namikawa
- Avian Bioscience Research Center, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan
| | - Yoichi Matsuda
- Avian Bioscience Research Center, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan
- Laboratory of Animal Genetics, Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan
| |
Collapse
|
|
27
|
Gisser JM, Cohen AR, Yin H, Gariepy CE. A novel bidirectional interaction between endothelin-3 and retinoic acid in rat enteric nervous system precursors. PLoS One 2013; 8:e74311. [PMID: 24040226 PMCID: PMC3767828 DOI: 10.1371/journal.pone.0074311] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2012] [Accepted: 08/02/2013] [Indexed: 01/31/2023] Open
Abstract
BACKGROUND Signaling through the endothelin receptor B (EDNRB) is critical for the development of the enteric nervous system (ENS) and mutations in endothelin system genes cause Hirschsprung's aganglionosis in humans. Penetrance of the disease is modulated by other genetic factors. Mutations affecting retinoic acid (RA) signaling also produce aganglionosis in mice. Thus, we hypothesized that RA and endothelin signaling pathways may interact in controlling development of the ENS. METHODS Rat immunoselected ENS precursor cells were cultured with the EDNRB ligand endothelin-3, an EDNRB-selective antagonist (BQ-788), and/or RA for 3 or 14 days. mRNA levels of genes related to ENS development, RA- and EDNRB-signaling were measured at 3 days. Proliferating cells and cells expressing neuronal, glial, and myofibroblast markers were quantified. RESULTS Culture of isolated ENS precursors for 3 days with RA decreases expression of the endothelin-3 gene and that of its activation enzyme. These changes are associated with glial proliferation, a higher percentage of glia, and a lower percentage of neurons compared to cultures without RA. These changes are independent of EDNRB signaling. Conversely, EDNRB activation in these cultures decreases expression of RA receptors β and γ mRNA and affects the expression of the RA synthetic and degradative enzymes. These gene expression changes are associated with reduced glial proliferation and a lower percentage of glia in the culture. Over 14 days in the absence of EDNRB signaling, RA induces the formation of a heterocellular plexus replete with ganglia, glia and myofibroblasts. CONCLUSIONS A complex endothelin-RA interaction exists that coordinately regulates the development of rat ENS precursors in vitro. These results suggest that environmental RA may modulate the expression of aganglionosis in individuals with endothelin mutations.
Collapse
Affiliation(s)
- Jonathan M. Gisser
- The Center for Molecular and Human Genetics, the Research Institute at Nationwide Children’s Hospital, Columbus, Ohio, United States of America
- Department of Pediatrics, the Ohio State University, Columbus, Ohio, United States of America
| | - Ariella R. Cohen
- The Center for Molecular and Human Genetics, the Research Institute at Nationwide Children’s Hospital, Columbus, Ohio, United States of America
| | - Han Yin
- The Biostatistics Shared Resources, Nationwide Children’s Hospital, Columbus, Ohio, United States of America
| | - Cheryl E. Gariepy
- The Center for Molecular and Human Genetics, the Research Institute at Nationwide Children’s Hospital, Columbus, Ohio, United States of America
- Department of Pediatrics, the Ohio State University, Columbus, Ohio, United States of America
| |
Collapse
|
|
28
|
An XJ, Li YQ, Qu XY, Zhang J, Zhang LY, Wang M, Zhu L, Chen SY, Chen HX, Tu YT, Zhou YW, Huang CZ. Silencing endothelin-3 expression attenuates the malignant behaviors of human melanoma cells by regulating SPARC levels. ACTA ACUST UNITED AC 2013; 33:581-586. [PMID: 23904381 DOI: 10.1007/s11596-013-1162-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2012] [Revised: 04/26/2013] [Indexed: 11/29/2022]
Abstract
Endothelin-3 (ET-3) is aberrantly expressed in both metastatic melanoma tissues and cultured melanoma cells. Our previous work showed that ET-3 could promote survival of metastatic melanoma cells via its altered expression. In this study, we investigated the mechanisms responsible for these gene-induced phenotypes in melanoma cells. An ET-3 gene sequence-specific shRNA vector pLVTHM-ET3-RNAi was constructed and transfected into human malignant melanoma cells A375 and MMRU, and the resultant molecular events and cellular changes were examined. As compared with the empty-vector group, cell proliferation was slowed down, and the growth inhibition rates were 38.9% in A375 cells and 38.4% in MMRU cells after transfection. In addition, cell invasion capability was also inhibited, with a reduction of 62.2% in A375 cells and 54.3% in MMRU cells. The percentage of apoptotic cells was found to increase. Meanwhile, in both cell lines, secreted protein acidic and rich in cysteine (SPARC) levels were down-regulated together with inhibition of its upstream signaling molecule, NF-κB. Thus, the current results suggested that down-regulated expression of ET3 attenuates the malignant behaviors of human melanoma cells partially by decreasing the expression of SPARC and NF-κB.
Collapse
Affiliation(s)
- Xiang-Jie An
- Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Yan-Qiu Li
- Department of Dermatology, Zhongshan Hospital, Wuhan, 430033, China
| | - Xiao-Ying Qu
- Department of Dermatology, No.457 Airforce Hospital, Wuhan, 430012, China
| | - Jing Zhang
- Department of Dermatology, Wuhan General Hospital of Guangzhou Command, Wuhan, 430070, China
| | - Ling-Yun Zhang
- Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Ming Wang
- Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Li Zhu
- Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Si-Yuan Chen
- Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Hong-Xiang Chen
- Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Ya-Ting Tu
- Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Yu-Wen Zhou
- Department of Dermatology and Skin Science, University of British Columbia, Vancouver, V5Z 4E8, Canada.
| | - Chang-Zheng Huang
- Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
| |
Collapse
|
|
29
|
Tian M, Wang Y, Gu X, Feng C, Fang S, Hu X, Li N. Copy number variants in locally raised Chinese chicken genomes determined using array comparative genomic hybridization. BMC Genomics 2013; 14:262. [PMID: 23594354 PMCID: PMC3637819 DOI: 10.1186/1471-2164-14-262] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2012] [Accepted: 04/15/2013] [Indexed: 11/10/2022] Open
Abstract
Background Copy number variants contribute to genetic variation in birds. Analyses of copy number variants in chicken breeds had focused primarily on those from commercial varieties with nothing known about the occurrence and diversity of copy number variants in locally raised Chinese chicken breeds. To address this deficiency, we characterized copy number variants in 11 chicken breeds and compared the variation among these breeds. Results We presented a detailed analysis of the copy number variants in locally raised Chinese chicken breeds identified using a customized comparative genomic hybridization array. We identified 833 copy number variants contained within 308 copy number variant regions. The median and mean sizes of the copy number variant regions were 14.6 kb and 35.1 kb, respectively. Of the copy number variant regions, 138 (45%) involved gain of DNA, 159 (52%) involved loss of DNA, and 11 (3%) involved both gain and loss of DNA. Principal component analysis and agglomerative hierarchical clustering revealed the close relatedness of the four locally raised chicken breeds, Shek-Ki, Langshan, Qingyuan partridge, and Wenchang. Biological process enrichment analysis of the copy number variant regions confirmed the greater variation among the four aforementioned varieties than among the seven other breeds studied. Conclusion Our description of the distribution of the copy number variants and comparison of the differences among the copy number variant regions of the 11 chicken breeds supplemented the information available concerning the copy number variants of other Chinese chicken breeds. In addition to its relevance for functional analysis, our results provided the first insight into how chicken breeds can be clustered on the basis of their genomic copy number variation.
Collapse
|
|
30
|
Liao S, Shang J, Tian X, Fan X, Shi X, Pei S, Wang Q, Yu B. Up-regulation of melanin synthesis by the antidepressant fluoxetine. Exp Dermatol 2012; 21:635-7. [PMID: 22776001 DOI: 10.1111/j.1600-0625.2012.01531.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Fluoxetine, a member of the class of selective serotonin reuptake inhibitors, is a potent antidepressant commonly used in clinical practice. Here, we report that fluoxetine increases cellular tyrosinase (TYR) activity, enhances the protein levels of microphthalmia-associated transcription factor (MITF), TYR and tyrosinase-related protein-1 (TRP-1) and eventually leads to a dramatic increase in melanin production in both murine B16F10 melanoma cells and normal human melanocytes (NHMCs). In well-characterized C57BL/6 mouse models, systemic application of fluoxetine increased hair pigmentation by up-regulating hair follicular MITF, TYR, TRP-1 and tyrosinase-related protein-2 (TRP-2) protein levels. Using a serotonin 1A receptor (SR1A) antagonist and RNA interference (RNAi) technique, we revealed that SR1A appears to be one of the involved pathways in the fluoxetine-induced melanogenesis in B16F10 cells. These results suggest that fluoxetine may hold a significant therapeutic potential for treating skin hypopigmentation disorders, and SR1A may serve as a novel target in modulating melanogenesis.
Collapse
Affiliation(s)
- Sha Liao
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, China
| | | | | | | | | | | | | | | |
Collapse
|
|
31
|
Dupin E, Coelho-Aguiar JM. Isolation and differentiation properties of neural crest stem cells. Cytometry A 2012; 83:38-47. [PMID: 22837061 DOI: 10.1002/cyto.a.22098] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2012] [Revised: 06/07/2012] [Accepted: 06/15/2012] [Indexed: 12/26/2022]
Abstract
A wide array of neural and non-neural cell types arises from the neural crest during vertebrate embryogenesis. The neural crest forms transiently in the dorsal neural primordium to yield migratory cells that will invade nearly all tissues and later, differentiate into bones and cartilages, vascular smooth muscle cells, connective tissues, neurons and glial cells of the peripheral nervous system, endocrine cells, and melanocytes. Due to the amazingly diversified array of cell types they generate, the neural crest cells represent an attractive model in the stem cell field. We review here in vivo and in vitro studies of individual cells, which led to the discovery and characterization of neural crest progenitors endowed with multipotency and stem cell properties. We also present an overview of the diverse types, marker expression, and locations of the neural crest-derived stem cells identified in the vertebrate body, with emphasis on those evidenced recently in mammalian adult tissues.
Collapse
Affiliation(s)
- Elisabeth Dupin
- Department of Developmental Biology, Institut de la Vision, Research Center UMR INSERM S968/CNRS 7210, 17 Rue Moreau, 75012 Paris, France.
| | | |
Collapse
|
|
32
|
Abstract
The neural crest is a multipotent and migratory cell type that forms transiently in the developing vertebrate embryo. These cells emerge from the central nervous system, migrate extensively and give rise to diverse cell lineages including melanocytes, craniofacial cartilage and bone, peripheral and enteric neurons and glia, and smooth muscle. A vertebrate innovation, the gene regulatory network underlying neural crest formation appears to be highly conserved, even to the base of vertebrates. Here, we present an overview of important concepts in the neural crest field dating from its discovery 150 years ago to open questions that will motivate future research.
Collapse
|
|
33
|
Pavan WJ, Raible DW. Specification of neural crest into sensory neuron and melanocyte lineages. Dev Biol 2012; 366:55-63. [PMID: 22465373 PMCID: PMC3351495 DOI: 10.1016/j.ydbio.2012.02.038] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2012] [Accepted: 02/29/2012] [Indexed: 11/27/2022]
Abstract
Elucidating the mechanisms by which multipotent cells differentiate into distinct lineages is a common theme underlying developmental biology investigations. Progress has been made in understanding some of the essential factors and pathways involved in the specification of different lineages from the neural crest. These include gene regulatory networks involving transcription factor hierarchies and input from signaling pathways mediated from environmental cues. In this review, we examine the mechanisms for two lineages that are derived from the neural crest, peripheral sensory neurons and melanocytes. Insights into the specification of these cell types may reveal common themes in the specification processes that occur throughout development.
Collapse
Affiliation(s)
- William J Pavan
- Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
| | | |
Collapse
|
|
34
|
Rodrigues FS, Doughton G, Yang B, Kelsh RN. A novel transgenic line using the Cre-lox system to allow permanent lineage-labeling of the zebrafish neural crest. Genesis 2012; 50:750-7. [DOI: 10.1002/dvg.22033] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2012] [Accepted: 04/12/2012] [Indexed: 12/22/2022]
|
|
35
|
Insights into Stem Cell Factor chemotactic guidance of neural crest cells revealed by a real-time directionality-based assay. Eur J Cell Biol 2012; 91:375-90. [DOI: 10.1016/j.ejcb.2011.12.007] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2011] [Revised: 12/19/2011] [Accepted: 12/20/2011] [Indexed: 11/23/2022] Open
|
|
36
|
Dupin E, Sommer L. Neural crest progenitors and stem cells: from early development to adulthood. Dev Biol 2012; 366:83-95. [PMID: 22425619 DOI: 10.1016/j.ydbio.2012.02.035] [Citation(s) in RCA: 167] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2012] [Accepted: 02/29/2012] [Indexed: 01/09/2023]
Abstract
In the vertebrate embryo, the neural crest forms transiently in the dorsal neural primordium to yield migratory cells that will invade nearly all tissues and later, will differentiate into bones and cartilages, neurons and glia, endocrine cells, vascular smooth muscle cells and melanocytes. Due to the amazingly diversified array of cell types it produces, the neural crest is an attractive model system in the stem cell field. We present here in vivo and in vitro studies of single cell fate, which led to the discovery and the characterization of stem cells in the neural crest of avian and mammalian embryos. Some of the key issues in neural crest cell diversification are discussed, such as the time of segregation of mesenchymal vs. neural/melanocytic lineages, and the origin and close relationships between the glial and melanocytic lineages. An overview is also provided of the diverse types of neural crest-like stem cells and progenitors, recently identified in a growing number of adult tissues in animals and humans. Current and future work, in which in vivo lineage studies and the use of injury models will complement the in vitro culture analysis, should help in unraveling the properties and function of neural crest-derived progenitors in development and disease.
Collapse
Affiliation(s)
- Elisabeth Dupin
- INSERM U894 Equipe Plasticité Gliale, Centre de Psychiatrie et de Neuroscience, 2 ter Rue d'Alésia 75014 Paris, France.
| | | |
Collapse
|
|
37
|
|
|
38
|
A complex genomic rearrangement involving the endothelin 3 locus causes dermal hyperpigmentation in the chicken. PLoS Genet 2011; 7:e1002412. [PMID: 22216010 PMCID: PMC3245302 DOI: 10.1371/journal.pgen.1002412] [Citation(s) in RCA: 118] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2011] [Accepted: 10/22/2011] [Indexed: 02/03/2023] Open
Abstract
Dermal hyperpigmentation or Fibromelanosis (FM) is one of the few examples of skin pigmentation phenotypes in the chicken, where most other pigmentation variants influence feather color and patterning. The Silkie chicken is the most widespread and well-studied breed displaying this phenotype. The presence of the dominant FM allele results in extensive pigmentation of the dermal layer of skin and the majority of internal connective tissue. Here we identify the causal mutation of FM as an inverted duplication and junction of two genomic regions separated by more than 400 kb in wild-type individuals. One of these duplicated regions contains endothelin 3 (EDN3), a gene with a known role in promoting melanoblast proliferation. We show that EDN3 expression is increased in the developing Silkie embryo during the time in which melanoblasts are migrating, and elevated levels of expression are maintained in the adult skin tissue. We have examined four different chicken breeds from both Asia and Europe displaying dermal hyperpigmentation and conclude that the same structural variant underlies this phenotype in all chicken breeds. This complex genomic rearrangement causing a specific monogenic trait in the chicken illustrates how novel mutations with major phenotypic effects have been reused during breed formation in domestic animals. The process of animal domestication has been a long and ongoing effort of the human race to cultivate beneficial traits in agriculturally productive or otherwise beneficial species. We are just now beginning to understand the effect this type of selection pressure has had on genetic variation and overall genome architecture using quickly advancing modern genetic and genomic technologies. Here we show how along the path of animal domestication a single large rearrangement involving a duplication and inversion of two distinct regions of the chicken genome occurred, likely disrupting long-range cis-regulatory elements of endothelin 3 (EDN3) and resulting in a very extreme skin pigmentation phenotype. Dermal hyperpigmentation, or Fibromelanosis (FM), is a defining characteristic of the Silkie chicken breed, which originates in China. Chickens very similar to the Silkie have been described in ancient Chinese texts on traditional medicine, illustrating how unique phenotypes in domesticated animals are incorporated into human culture and tradition that persists to this day. The presence of the same rearrangement in other FM chicken breeds found around the world highlights both the causality of this mutation as well as how humans serve to spread genetic variation linked to novel traits in domestic animals.
Collapse
|
|
39
|
Gene duplication of endothelin 3 is closely correlated with the hyperpigmentation of the internal organs (Fibromelanosis) in silky chickens. Genetics 2011; 190:627-38. [PMID: 22135351 DOI: 10.1534/genetics.111.136705] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
During early development in vertebrates, pluripotent cells are generated from the neural crest and migrate according to their presumptive fate. In birds and mammals, one of the progeny cells, melanoblasts, generally migrate through a dorsolateral route of the trunk region and differentiate to melanocytes. However, Silky is an exceptional chicken in which numerous melanoblasts travel via a ventral pathway and disperse into internal organs. Finally, these ectopic melanocytes induce heavy dermal and visceral melanization known as Fibromelanosis (Fm). To identify the genetic basis of this phenotype, we confirmed the mode of inheritance of Fm as autosomal dominant and then performed linkage analysis with microsatellite markers and sequence-tagged site markers. Using 85 backcross progeny from crossing Black Minorca chickens (BM-C) with F(1) individuals between White Silky (WS) and BM-C Fm was located on 10.2-11.7 Mb of chicken chromosome 20. In addition, we noticed a DNA marker that all Silky chickens and the F(1) individuals showed heterozygous genotyping patterns, suggesting gene duplication in the Fm region. By quantitative real-time PCR assay, Silky line-specific gene duplication was detected as an ~130-kb interval. It contained five genes including endothelin 3 (EDN3), which encoded a potent mitogen for melanoblasts/melanocytes. EDN3 with another three of these duplicated genes in Silky chickens expressed almost twofold of those in BM-C. Present results strongly suggest that the increase of the expression levels resulting from the gene duplication in the Fm region is the trigger of hypermelanization in internal organs of Silky chickens.
Collapse
|
|
40
|
Liu Y, Ye F, Yamada K, Tso JL, Zhang Y, Nguyen DH, Dong Q, Soto H, Choe J, Dembo A, Wheeler H, Eskin A, Schmid I, Yong WH, Mischel PS, Cloughesy TF, Kornblum HI, Nelson SF, Liau LM, Tso CL. Autocrine endothelin-3/endothelin receptor B signaling maintains cellular and molecular properties of glioblastoma stem cells. Mol Cancer Res 2011; 9:1668-85. [PMID: 22013079 DOI: 10.1158/1541-7786.mcr-10-0563] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Glioblastoma stem cells (GSC) express both radial glial cell and neural crest cell (NCC)-associated genes. We report that endothelin 3 (EDN3), an essential mitogen for NCC development and migration, is highly produced by GSCs. Serum-induced proliferative differentiation rapidly decreased EDN3 production and downregulated the expression of stemness-associated genes, and reciprocally, two glioblastoma markers, EDN1 and YKL-40 transcripts, were induced. Correspondingly, patient glioblastoma tissues express low levels of EDN3 mRNA and high levels of EDN1 and YKL-40 mRNA. Blocking EDN3/EDN receptor B (EDNRB) signaling by an EDNRB antagonist (BQ788), or EDN3 RNA interference (siRNA), leads to cell apoptosis and functional impairment of tumor sphere formation and cell spreading/migration in culture and loss of tumorigenic capacity in animals. Using exogenous EDN3 as the sole mitogen in culture does not support GSC propagation, but it can rescue GSCs from undergoing cell apoptosis. Molecular analysis by gene expression profiling revealed that most genes downregulated by EDN3/EDNRB blockade were those involved in cytoskeleton organization, pause of growth and differentiation, and DNA damage response, implicating the involvement of EDN3/EDNRB signaling in maintaining GSC migration, undifferentiation, and survival. These data suggest that autocrine EDN3/EDNRB signaling is essential for maintaining GSCs. Incorporating END3/EDNRB-targeted therapies into conventional cancer treatments may have clinical implication for the prevention of tumor recurrence.
Collapse
Affiliation(s)
- Yue Liu
- Department of Surgery/Surgical Oncology, University of California Los Angeles, Los Angeles, California 90095, USA
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
41
|
Abstract
A highly enriched population of neural crest cells (NCCs) from amniote embryos, such as from chicks, mice and humans, is desirable for experiments in fate determination. NCCs are also useful for testing the functional effects of molecular changes underlying numerous human diseases of neural crest derivatives and for investigating their potential for therapeutic compensation. This protocol details embryonic microdissection followed by neural tube explantation. Conditions favoring NCC expansion and the maintenance of their stem cell-like properties are described. Although neural crest-like cells can be derived from a number of sites in the mature organism, full potential is best ensured by their purification from their source tissue at the outset of migration. Going from embryo to established cell line takes 4 d; the first is the most labor-intensive day, but minimal intervention is required thereafter.
Collapse
Affiliation(s)
- Heather Etchevers
- Institut National de Santé et de Recherche Médicale (INSERM) U910, Université de Méditerranée Faculté de Médecine, Marseille, France.
| |
Collapse
|
|
42
|
Mohlin SA, Wigerup C, Påhlman S. Neuroblastoma aggressiveness in relation to sympathetic neuronal differentiation stage. Semin Cancer Biol 2011; 21:276-82. [PMID: 21945591 DOI: 10.1016/j.semcancer.2011.09.002] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2011] [Accepted: 09/08/2011] [Indexed: 01/01/2023]
Abstract
Neuroblastoma is a childhood malignancy of the sympathetic neuronal lineage. It is a rare disease, but since it is frequently diagnosed during infancy, neuroblastoma causes life-long medical follow up of those children that survive the disease. It was early recognized that a high tumor cell differentiation stage correlates to favorable clinical stage and positive clinical outcome. Today, highly differentiated tumors are surgically removed and not further treated. Cells of many established human neuroblastoma cell lines have the capacity to differentiate when stimulated properly, and these cell lines have been used as models for studying and understanding central concepts of tumor cell differentiation. One recent aspect of this issue is the observation that tumor cells can dedifferentiate and gain a stem cell-like phenotype during hypoxic conditions, which was first shown in neuroblastoma. Aberrant or blocked differentiation is a central aspect of neuroblastoma genesis. In this review we summarize known genetic and non-genetic events in neuroblastoma that might be coupled to an aberrant sympathetic neuronal differentiation and thereby indirectly influencing tumorigenesis and/or aggressive neuroblastoma behavior.
Collapse
Affiliation(s)
- Sofie A Mohlin
- Center for Molecular Pathology, Department of Laboratory Medicine, CREATE Health, Lund University, Skåne University Hospital, Malmö, Sweden
| | | | | |
Collapse
|
|
43
|
Motohashi T, Yamanaka K, Chiba K, Miyajima K, Aoki H, Hirobe T, Kunisada T. Neural crest cells retain their capability for multipotential differentiation even after lineage-restricted stages. Dev Dyn 2011; 240:1681-93. [PMID: 21594952 DOI: 10.1002/dvdy.22658] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/17/2011] [Indexed: 11/06/2022] Open
Abstract
Multipotency of neural crest cells (NC cells) is thought to be a transient phase at the early stage of their generation; after NC cells emerge from the neural tube, they are specified into the lineage-restricted precursors. We analyzed the differentiation of early-stage NC-like cells derived from Sox10-IRES-Venus ES cells, where the expression of Sox10 can be visualized with a fluorescent protein. Unexpectedly, both the Sox10+/Kit- cells and the Sox10+/Kit+ cells, which were restricted in vivo to the neuron (N)-glial cell (G) lineage and melanocyte (M) lineage, respectively, generated N, G, and M, showing that they retain multipotency. We generated mice from the Sox10-IRES-Venus ES cells and analyzed the differentiation of their NC cells. Both the Sox10+/Kit- cells and Sox10+/Kit+ cells isolated from these mice formed colonies containing N, G, and M, showing that they are also multipotent. These findings suggest that NC cells retain multipotency even after the initial lineage-restricted stages.
Collapse
Affiliation(s)
- Tsutomu Motohashi
- Department of Tissue and Organ Development, Regeneration, and Advanced Medical Science, Gifu University Graduate School of Medicine, CREST-JST, Gifu, Japan.
| | | | | | | | | | | | | |
Collapse
|
|
44
|
Kawasaki-Nishihara A, Nishihara D, Nakamura H, Yamamoto H. ET3/Ednrb2 signaling is critically involved in regulating melanophore migration in Xenopus. Dev Dyn 2011; 240:1454-66. [DOI: 10.1002/dvdy.22649] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/01/2011] [Indexed: 01/19/2023] Open
|
|
45
|
Spica T, Fargnoli MC, Hetet G, Bertrand G, Formicone F, Descamps V, Wolkenstein P, Dupin N, Lebbe C, Basset-Seguin N, Saiag P, Cambien F, Grandchamp B, Peris K, Soufir N. EDNRB gene variants and melanoma risk in two southern European populations. Clin Exp Dermatol 2011; 36:782-7. [PMID: 21507037 DOI: 10.1111/j.1365-2230.2011.04062.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
BACKGROUND EDNRB gene variants were reported to be associated with melanoma risk in French patients, with the S305N variant showing the highest frequency. AIM To verify the S305N association with melanoma risk in an independent larger French population (378 patients, 389 controls); to investigate the role of EDNRB variants in melanoma risk in an Italian population (133 patients, 118 controls); and to explore the association of CDKN2A or CDK4 mutations with the S305N EDNRB variant in a subgroup of patients (59 French, 12 Italian) with a suspected hereditary predisposition to melanoma (familial melanoma, sporadic multiple primary melanoma or melanoma associated with pancreatic cancer). METHODS The S305N variant was genotyped in the French population, while the EDNRB gene in the Italian population was entirely sequenced. RESULTS Overall, there was no significant difference in the frequency of the S305N variant between patients with sporadic melanoma and controls in either the French or the Italian population. However, a significantly higher S305N allele frequency was detected in French patients with a suspected hereditary predisposition to melanoma compared with controls (P = 0.04). In addition, in this subgroup of patients, the S305N allele was also significantly associated with the presence of CDKN2A mutations (P = 0.04). CONCLUSIONS Our results showed no evidence of association of the S305N EDNRB polymorphism with sporadic melanoma risk in either the French or Italian populations, but there was an indication that EDNRB might be a melanoma-predisposing gene in French patients with a suspected hereditary predisposition to melanoma.
Collapse
Affiliation(s)
- T Spica
- Department of Dermatology, University of L'Aquila, L'Aquila, Italy
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
46
|
Dupin E. [Phenotypic plasticity of neural crest-derived melanocytes and Schwann cells]. Biol Aujourdhui 2011; 205:53-61. [PMID: 21501576 DOI: 10.1051/jbio/2011008] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2011] [Indexed: 12/23/2022]
Abstract
Melanocytes, the pigmented cells of the skin, and the glial Schwann cells lining peripheral nerves are developmentally derived from an early and transient ectodermal structure of the vertebrate embryo, the neural crest, which is also at the origin of multiple neural and non-neural cell types. Besides melanocytes and neural cells of the peripheral nervous system, the neural crest cells give rise to mesenchymal cell types in the head, which form most of the craniofacial skeleton, dermis, fat tissue and vascular musculo-connective components. How such a wide diversity of differentiation fates is established during embryogenesis and is later maintained in adult tissues are among key questions in developmental and stem cell biology. The analysis of the developmental potentials of single neural crest cells cultured in vitro led to characterizing multipotent stem/progenitor cells as well as more restricted precursors in the early neural crest of avian and mammalian embryos. Data support a hierarchical model of the diversification of neural crest lineages through progressive restrictions of multipotent stem cell potentials driven by local environmental factors. In particular, melanocytes and glial Schwann cells were shown to arise from a common bipotent progenitor, which depends upon the peptide endothelin-3 for proliferation and self-renewal ability. In vivo, signaling by endothelin-3 and its receptor is also required for the early development of melanocytes and proper pigmentation of the vertebrate body. It is generally assumed that, after lineage specification and terminal differentiation, specialized cell types, like the melanocytes and Schwann cells, do not change their identity. However, this classic notion that somatic cell differentiation is a stable and irreversible process has been challenged by emerging evidence that dedifferentiation can occur in different biological systems through nuclear transfer, cell fusion, epigenetic modifications and ectopic gene expression. This review considers the issue of whether neural crest-derived lineages are endowed with some phenotypic plasticity. Emphasis is put on the ability of pigment cells and Schwann cells to dedifferentiate and reprogram their fate in vitro. To address this question, we have studied the clonal progeny of differentiated Schwann cells and melanocytes after their isolation from the sciatic nerve and the back skin of quail embryos, respectively. When stimulated to proliferate in vitro in the presence of endothelin-3, both cell types were able to dedifferentiate and produce alternative neural crest-derived cell lineages. Individual Schwann cells isolated by FACS, using a glial-specific surface marker, gave rise in culture to pigment cells and myofibroblasts/smooth muscle cells. Treatment of the cultures with endothelin-3 was required for Schwann cell conversion into melanocytes, which involved acquisition of multipotency. Moreover, Schwann cell plasticity could also be induced in vivo: following transplantation into the branchial arch of a young chick host embryo, dedifferentiating Schwann cells were able to integrate the forming head structures of the host and, specifically, to contribute smooth muscle cells to the wall of cranial blood vessels. We also analyzed the in vitro behavior of individual pigment cells obtained by microdissection and enzymatic treatment of quail epidermis at embryonic and hatching stages. In single cell cultures treated with endothelin-3, pigment cells strongly proliferated while rapidly dedifferentiating into unpigmented cells, leading to the formation of large colonies that comprised glial cells and myofibroblasts in addition to melanocytes. By serially subcloning these primary colonies, we could efficiently propagate a bipotent glial-melanocytic precursor that is generated in the progeny of the melanocytic founder. These data therefore suggest that pigment cells have the ability to revert back to the state of self-renewing neural crest-like progenitors. Altogether, these studies have shown that Schwann cells and pigment cells display an unstable status of differentiation, which can be disclosed if these differentiated cells are displaced out of their native tissue. When challenged with new environmental conditions in vitro, differentiated Schwann cells and pigment cells can reacquire stem cell properties of their neural crest ancestors. Notably, such reprogramming was achieved through the effect of a single exogenous factor and without the need of any induced genetic modification. Deciphering the cellular and molecular mechanisms that regulate the plasticity and maintenance of neural crest-derived differentiated cells is likely to be an important step towards the understanding of the neurocristopathies and cancers that target neural crest derivatives in humans.
Collapse
Affiliation(s)
- Elisabeth Dupin
- Inserm U894 Equipe Plasticité gliale, Centre Psychiatrie et Neurosciences, 2 ter rue d'Alésia, 75014 Paris, France.
| |
Collapse
|
|
47
|
Abstract
The neural crest is a transient structure in vertebrate embryos that generates multiple neural and mesenchymal cell types as well as melanocytes. Melanocytes in the skin either derive directly from neural crest cells populating the skin via a dorsolateral migratory pathway or arise by detaching from nerves innervating the skin. Several transcription factors, such as FoxD3, Sox10, Pax3, and Mitf, take part in a genetic network regulating melanocyte formation from the neural crest. The activity of these intrinsic factors is controlled and modulated by extracellular signals including canonical Wnt, Edn, Kitl, and other signals that remain to be identified. Here, we summarize the current view of how melanocytes are specified from the neural crest and put this process into the context of spatiotemporal lineage decisions in neural crest cells.
Collapse
Affiliation(s)
- Lukas Sommer
- Cell and Developmental Biology, Institute of Anatomy, University of Zurich, Winterthurerstrasse, Zurich, Switzerland.
| |
Collapse
|
|
48
|
Kobayashi NR, Hawes SM, Crook JM, Pébay A. G-protein coupled receptors in stem cell self-renewal and differentiation. Stem Cell Rev Rep 2010; 6:351-66. [PMID: 20625855 DOI: 10.1007/s12015-010-9167-9] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Stem cells have great potential for understanding early development, treating human disease, tissue trauma and early phase drug discovery. The factors that control the regulation of stem cell survival, proliferation, migration and differentiation are still emerging. Some evidence now exists demonstrating the potent effects of various G-protein coupled receptor (GPCR) ligands on the biology of stem cells. This review aims to give an overview of the current knowledge of the regulation of embryonic and somatic stem cell maintenance and differentiation by GPCR ligands.
Collapse
|
|
49
|
Adameyko I, Lallemend F. Glial versus melanocyte cell fate choice: Schwann cell precursors as a cellular origin of melanocytes. Cell Mol Life Sci 2010; 67:3037-55. [PMID: 20454996 PMCID: PMC11115498 DOI: 10.1007/s00018-010-0390-y] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2010] [Revised: 04/20/2010] [Accepted: 04/26/2010] [Indexed: 12/12/2022]
Abstract
Melanocytes and Schwann cells are derived from the multipotent population of neural crest cells. Although both cell types were thought to be generated through completely distinct pathways and molecular processes, a recent study has revealed that these different cell types are intimately interconnected far beyond previously postulated limits in that they share a common post-neural crest progenitor, i.e. the Schwann cell precursor. This finding raises interesting questions about the lineage relationships of hitherto unrelated cell types such as melanocytes and Schwann cells, and may provide clinical insights into mechanisms of pigmentation disorders and for cancer involving Schwann cells and melanocytes.
Collapse
Affiliation(s)
- Igor Adameyko
- Unit of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Scheeles väg 1-A1-plan2, 171 77 Stockholm, Sweden
| | - Francois Lallemend
- Unit of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Scheeles väg 1-A1-plan2, 171 77 Stockholm, Sweden
| |
Collapse
|
|
50
|
Ernfors P. Cellular origin and developmental mechanisms during the formation of skin melanocytes. Exp Cell Res 2010; 316:1397-407. [PMID: 20211169 DOI: 10.1016/j.yexcr.2010.02.042] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2010] [Accepted: 02/28/2010] [Indexed: 11/20/2022]
Abstract
Melanocytes are derived from the neural crest (NC), which are transient multipotent cells arising by delamination from the developing dorsal neural tube. During recent years, signaling systems and molecular mechanisms of melanocyte development have been studied in detail, but the exact diversification of the NC into melanocytes and how they migrate, expand and disperse in the skin have not been fully understood. The recent finding that Schwann cell precursors (SCPs) of the growing nerve represents a stem cell niche from which various cell types, including Schwann cells, endoneural fibroblasts and melanocytes arise has exposed new knowledge on the cellular basis for melanocyte development. This opens for the identification of new factors and reinterpretation of old data on cell fate instructive, proliferative, survival and cell homing factors participating in melanocyte development.
Collapse
Affiliation(s)
- Patrik Ernfors
- Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, 17177 Stockholm, Sweden.
| |
Collapse
|