• biochemistry
• physiology
• diseases
• gastroenterology
• molecular medicine

• Hepatic Veno-Occlusive Disease/pathology
• Hepatic Veno-Occlusive Disease/metabolism
• Hepatic Veno-Occlusive Disease/chemically induced
• Animals
• Apoptosis
• Hepatocytes/metabolism
• Hepatocytes/pathology
• Humans
• Fas Ligand Protein/metabolism
• Fas Ligand Protein/genetics
• Mice
• Platelet Aggregation/drug effects
• Male
• Hep G2 Cells
• Disease Models, Animal
• Liver/pathology
• Liver/metabolism
• Blood Platelets/metabolism
• Monocrotaline

• 20K07323 Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan
• 20K09029 Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan
• 21H02695 Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan

• Angiogenesis
• Biomimetic
• Microphysiological

• 2021321384 National Science Foundation Graduate Research Fellowship Program

• TGFβ1
• liver regeneration
• platelets

• Animals
• Liver Regeneration/physiology
• Transforming Growth Factor beta1/metabolism
• Transforming Growth Factor beta1/genetics
• Hepatectomy
• Mice
• Mice, Knockout
• Blood Platelets/metabolism
• Thrombopoietin/metabolism
• Interleukin-6/metabolism
• Interleukin-6/genetics
• Cell Proliferation
• Hepatocyte Growth Factor/metabolism
• Hepatocyte Growth Factor/genetics
• Liver/metabolism
• Hepatocytes/metabolism
• Male
• Platelet Factor 4/metabolism
• Platelet Factor 4/genetics
• Mice, Inbred C57BL

• CRSK-3_196301 Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (SNF)

• Clinical application
• clinical trial
• drug therapy
• hepatocyte growth factor
• neuroprotective factor
• regenerative medicine
• spinal cord injury

• Spinal Cord Injuries/drug therapy
• Spinal Cord Injuries/physiopathology
• Hepatocyte Growth Factor/pharmacology
• Hepatocyte Growth Factor/metabolism
• Animals
• Humans
• Neuroprotective Agents/pharmacology
• Neuroprotective Agents/administration & dosage
• Regenerative Medicine/methods
• Disease Models, Animal
• Nerve Regeneration/drug effects
• Drug Development

• Hybrid model
• Individual-based model
• Tumor invasion
• Tumor morphology

• Humans
• Neoplasms/metabolism
• Oxygen/metabolism
• Models, Biological
• Extracellular Matrix/metabolism

• Endometrial thickness
• Frozen embryo transfer
• Platelet-rich plasma
• Thin endometrium
• Thin lining

• Pregnancy
• Humans
• Female
• Abortion, Spontaneous/epidemiology
• Cohort Studies
• Embryo Transfer
• Pregnancy Rate
• Endometrium/physiology
• Platelet-Rich Plasma
• Retrospective Studies

• Epidemiology
• Hepatocyte growth factor
• Physical activity

• Humans
• Cell Cycle
• Cell Division
• Neoplasms/drug therapy
• Neoplasms/genetics
• Antineoplastic Agents/pharmacology
• Antineoplastic Agents/therapeutic use
• Cyclin-Dependent Kinases
• Cell Proliferation

The liver has remarkable regenerative potential, with the capacity to regenerate after 75% hepatectomy in humans and up to 90% hepatectomy in some rodent models, enabling it to meet the challenge of diverse injury types, including physical trauma, infection, inflammatory processes, direct toxicity, and immunological insults. Current understanding of liver regeneration is based largely on animal research, historically in large animals, and more recently in rodents and zebrafish, which provide powerful genetic manipulation experimental tools. Whilst immensely valuable, these models have limitations in extrapolation to the human situation. In vitro models have evolved from 2-dimensional culture to complex 3 dimensional organoids, but also have shortcomings in replicating the complex hepatic micro-anatomical and physiological milieu. The process of liver regeneration is only partially understood and characterized by layers of complexity. Liver regeneration is triggered and controlled by a multitude of mitogens acting in autocrine, paracrine, and endocrine ways, with much redundancy and cross-talk between biochemical pathways. The regenerative response is variable, involving both hypertrophy and true proliferative hyperplasia, which is itself variable, including both cellular phenotypic fidelity and cellular trans-differentiation, according to the type of injury. Complex interactions occur between parenchymal and non-parenchymal cells, and regeneration is affected by the status of the liver parenchyma, with differences between healthy and diseased liver. Finally, the process of termination of liver regeneration is even less well understood than its triggers. The complexity of liver regeneration biology combined with limited understanding has restricted specific clinical interventions to enhance liver regeneration. Moreover, manipulating the fundamental biochemical pathways involved would require cautious assessment, for fear of unintended consequences. Nevertheless, current knowledge provides guiding principles for strategies to optimise liver regeneration potential.

• Liver
• Liver regeneration potential
• Regeneration biology
• Tumour
• Therapies

Despite years of positive animal data, hepatocyte growth factor (HGF) has never been developed into a useful pharmaceutical, primarily due to its poor pharmacological properties. CM1021 is a fusion protein containing the K1 loop of HGF and the human IgG1 Fc region. The experiments described here demonstrate that CM1021 has the biological properties of HGF and the pharmacological properties of a monoclonal antibody. CM1021 stimulates scattering and branching morphogenesis in MDCK cells and stimulates liver growth in vivo. Unlike HGF, it is available via intraperitoneal injection and has an estimated half-life similar to an antibody.

•

Fusion of the K1 loop of HGF to the Fc region of IgG creates CM1021, a long half-life HGF mimetic.

• R01 CA251928 NCI NIH HHS
• R01 DK125396 NIDDK NIH HHS

• amyloid light-chains
• hepatocyte growth factor
• hyaluronic acid
• primary systemic amyloidosis

• cytoskeleton
• dendrite
• development
• growth cone
• spine

• R01 NS099405 NINDS NIH HHS
• R01 NS113314 NINDS NIH HHS
• R21 NS088477 NINDS NIH HHS
• R21 NS125419 NINDS NIH HHS

• Cavernous nerve
• Chitosan
• Erectile function
• Intracavernosal injection
• Platelet-rich plasma
• Radical prostatectomy

• Animals
• Chitosan
• Erectile Dysfunction/drug therapy
• Humans
• Male
• Platelet-Rich Plasma
• Rats

• bone marrow
• growth factors
• immunomodulators
• platelet-rich plasma
• platelets
• secretome

• Blood Platelets
• Bone Marrow
• Pilot Projects
• Platelet-Rich Plasma
• Vascular Endothelial Growth Factor A

This study aimed to assess the value of the hepatocyte growth factor (HGF) as an independent predictor of a Fontan circulation failure.

This retrospective case–control study included 34 consecutive patients (19 men and 15 women) who underwent a post‐operative cardiac catheterization after a Fontan operation at the Saitama Medical University International Medical Center between April 2017 and December 2019. We divided the patients into two groups according to the HGF level: HGF < 0.4 ng/mL (n = 20, normal HGF group) and HGF ≥ 0.4 ng/mL (n = 14, elevated HGF group). The age at the time of the cardiac catheterization was 59.3 ± 7.9 months. The range of the duration between the Fontan operation and the cardiac catheterization was 37.5 ± 7.9 months. The age (P = 0.417), gender (P = 0.08), morphology of the functional ventricle (P = 0.99), presence or closure of the Fontan fenestration (P = 0.704), and rate of medication use (angiotensin‐converting enzyme inhibitors or angiotensin II receptor blockers) (P = 0.99) were equivalent between the two groups. Laboratory parameters including the brain natriuretic peptide level (P = 0.085), serum creatinine level (P = 0.27), and aspartate aminotransferase level (P = 0.235) were similar between the two groups. The elevated HGF group had a higher C‐reactive protein level than the normal HGF group (0.42 ± 0.14 and 0.05 ± 0.01 mg/dL, P = 0.005). The elevated HGF group had a higher central venous pressure (CVP) level than the normal HGF group (13.4 ± 0.7 and 9.7 ± 0.4 mmHg, P < 0.0001), and the HGF was positively correlated with the CVP (P = 0.0004, r² = 0.33). The SvO₂ level was significantly lower in the elevated HGF group than in the normal HGF group (61.9 ± 2.3% and 75.0 ± 1.2%, P < 0.0001), and the HGF was negatively correlated with the SvO₂ (P < 0.0001, r² = 0.65). Of the 34 patients, six underwent catheter interventions. Patients who underwent catheter interventions had a higher HGF level than those who did not (0.44 ± 0.03 and 0.37 ± 0.01 ng/mL, P = 0.032). The receiver operating characteristic curve created for the discrimination of a catheter intervention revealed that an HGF value of >0.405 ng/mL could detect the need for a catheter intervention with 75.0% sensitivity and 83.3% specificity. A multivariable regression analysis showed that an elevated HGF was an independent predictor of an elevated CVP (β‐coefficient 21.2, SE 5.5, P = 0.0005) and decreased SvO₂ (β‐coefficient −92.9, SE 12.4, P < 0.0001).

The HGF is an independent predictor of a failure of a Fontan circulation. The HGF is an indicator for an additional catheter intervention after a Fontan operation.

• EGFR-TKI
• Non-small cell lung cancer
• Overall survival
• Platelet
• Progression-free survival

• diabetic macular edema
• hepatocyte growth factor activator
• retinal vein occlusion
• vascular leakage

• P30 EY001765 NEI NIH HHS

• Extravasation
• Intravascular outgrowth
• Metastasis
• Platelets
• Tumor cell arrest

• Hepatectomy
• Humans
• Liver Failure/etiology
• Liver Function Tests
• Platelet Count
• Postoperative Complications/etiology
• Predictive Value of Tests
• Risk Factors
• Thrombocytopenia/complications

• Jagged1
• NOTCH
• hepatic progenitor cell
• hepatic stellate cell

Besides mediating hemostatic functions, platelets are increasingly recognized as important players of inflammation. Data from experiments in mice and men revealed various intersection points between thrombosis, hemostasis, and inflammation, which are addressed and discussed in this review in detail. One such example is the intrinsic coagulation cascade that is initiated after platelet activation thereby further propagating and re-enforcing wound healing or thrombus formation but also contributing to the pathophysiology of severe diseases. FXII of the intrinsic pathway connects platelet activation with the coagulation cascade during immune reactions. It can activate the contact system thereby either creating an inflammatory state or accelerating inflammation. Recent insights into platelet biology could show that platelets are equipped with complement receptors. Platelets are important for tissue remodeling after injury has been inflicted to the endothelial barrier and to the subendothelial tissue. Thus, platelets are increasingly recognized as more than just cells relevant for bleeding arrest. Future insights into platelet biology are to be expected. This research will potentially offer novel opportunities for therapeutic intervention in diseases featuring platelet abundance.

• EAE
• complement
• infection
• inflammation
• innate immunity
• platelets
• stroke
• tissue remodeling

• cancer evolution
• cell migration
• collective motility
• endocytosis

A growing body of evidence supports the role of platelets in cancer metastasis, escape from immune surveillance, and angiogenesis. Mean platelet volume (MPV), which reflects platelet turnover, is reported routinely as part of automated complete blood count. Accumulating evidence suggests that MPV is a useful biomarker in several diseases including cancer. However, its role in cancer patients receiving molecular targeted therapy has not been described in the literature.

We retrospectively analysed the prognostic impact of MPV in advanced or recurrent EGFR mutant lung adenocarcinoma treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs). Lymphocyte-to-monocyte ratio (LMR) has been previously reported to be a poor prognostic factor in EGFR mutant non-small cell lung cancer and was also included as a covariate.

Using the previously described Cutoff Finder algorithm, the cut-off points for MPV and LMR that best predicted progression free survival (PFS) of EGFR-TKI were determined as 10.3 and 2.8, respectively. The median PFS was 14.7 and 8.2 months in MPV low and high groups (p = 0.013, log-rank test). The median PFS was 13.5 and 6.2 months in LMR high and low groups (p < 0.001, log-rank test). MPV and LMR were independently distributed (chi square test) and the multivariate analysis using Cox’s proportional hazards regression model revealed that high MPV, low LMR, and pleural effusion were significant predictors for shorter PFS.

MPV and LMR, measured as part of routine complete blood count, can be utilized to predict the outcome of EGFR-TKI therapy with no additional costs. Our results suggest a mechanism of EGFR-TKI resistance which is associated with the functional status of the platelets.

• Adult
• Aged
• Aged, 80 and over
• Carcinoma, Non-Small-Cell Lung/blood
• Carcinoma, Non-Small-Cell Lung/drug therapy
• Carcinoma, Non-Small-Cell Lung/genetics
• ErbB Receptors/genetics
• Female
• Humans
• Lung Neoplasms/blood
• Lung Neoplasms/drug therapy
• Lung Neoplasms/genetics
• Lymphocyte Count
• Male
• Mean Platelet Volume
• Middle Aged
• Monocytes/cytology
• Mutation
• Prognosis
• Progression-Free Survival
• Protein Kinase Inhibitors/therapeutic use
• Retrospective Studies
• Treatment Outcome

• PD-L1, tumor microenvironment
• cancer
• hypoxia
• hypoxia-inducible factor
• immunotherapy
• immunotolerance
• unfolded protein response

• Diels et Gilg
• Epithelial mesenchymal transition
• Hepatocyte growth factor
• Isoquercitrin

• angiogenesis
• gene therapy
• hepatocyte growth factor

Head and neck squamous cell carcinoma (HNSCC) is a highly morbid disease. Recent developments including Food and Drug Administration (FDA) approved molecular targeted agent’s pembrolizumab and cetuximab show promise but did not improve the five-year survival which is currently less than 40%. The hepatocyte growth factor receptor; also known as mesenchymal–epithelial transition factor (c-Met) and its ligand hepatocyte growth factor (HGF) are overexpressed in head and neck squamous cell carcinoma (HNSCC); and regulates tumor progression and response to therapy. The c-Met pathway has been shown to regulate many cellular processes such as cell proliferation, invasion, and angiogenesis. The c-Met pathway is involved in cross-talk, activation, and perpetuation of other signaling pathways, curbing the cogency of a blockade molecule on a single pathway. The receptor and its ligand act on several downstream effectors including phospholipase C gamma (PLCγ), cellular Src kinase (c-Src), phosphotidylinsitol-3-OH kinase (PI3K) alpha serine/threonine-protein kinase (Akt), mitogen activate protein kinase (MAPK), and wingless-related integration site (Wnt) pathways. They are also known to cross-talk with other receptors; namely epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) and specifically contribute to treatment resistance. Clinical trials targeting the c-Met axis in HNSCC have been undertaken because of significant preclinical work demonstrating a relationship between HGF/c-Met signaling and cancer cell survival. Here we focus on HGF/c-Met impact on cellular signaling in HNSCC to potentiate tumor growth and disrupt therapeutic efficacy. Herein we summarize the current understanding of HGF/c-Met signaling and its effects on HNSCC. The intertwining of c-Met signaling with other signaling pathways provides opportunities for more robust and specific therapies, leading to better clinical outcomes.

• c-Met
• head and neck squamous cell carcinoma
• hepatocyte growth factor
• receptor tyrosine kinase
• tumor microenvironment

Podoplanin/Aggrus, known as a platelet aggregation-inducing factor, is frequently overexpressed in lung squamous cell carcinomas (LSCC) and glioblastomas among other tumours, and its expression has been reported to be correlated with poor prognosis. However, the contribution of podoplanin to malignant progression has been elusive. Here we demonstrate that in podoplanin-positive LSCC cells, their growth was abrogated by podoplanin knockout in vivo but not in vitro. Conversely, ectopic expression of podoplanin promoted cell growth in vivo and facilitated intratumoral platelet activation. Consistently, LSCC cells evoked podoplanin-mediated platelet aggregation (PMPA), and the releasates from platelets during PMPA promoted the growth of LSCC cells in vitro. Phospho-receptor-tyrosine-kinase array analysis revealed that epidermal growth factor receptor (EGFR) phosphorylation of LSCC cells was responsible for the growth promotion induced by platelet releasates. Treatment with an antiplatelet agent or podoplanin-neutralizing antibody depressed the growth of an LSCC tumour xenograft via suppression of EGFR phosphorylation. These results suggested that podoplanin in LSCC enhanced cell growth by inducing PMPA in vivo and contributed to malignant progression.

Obesity and its associated chronic inflammation in adipose tissue initiate insulin resistance, which is related to several pathologies including hypertension and atherosclerosis. Previous reports demonstrated that circulating hepatocyte growth factor (HGF) level was associated with obesity and type 2 diabetes. However, its precise role in obesity and related-pathology is unclear. In this experiment, cardiac-specific over-expression of human HGF in mice (HGF-Tg mice) which showed 4–5 times higher serum HGF levels than wild-type mice were used. While body weight in wild-type mice fed with high fat diet (HFD) for 14 weeks was significantly increased accompanied with insulin resistance, HGF-Tg mice prevented body weight gain and insulin resistance. The accumulation of macrophages and elevated levels of inflammatory mediators in adipose tissue were significantly inhibited in HGF-Tg mice as compared to wild-type mice. The HFD-induced obesity in wild-type mice treated with HGF-neutralizing antibody showed an exacerbated response to the glucose tolerance test. These gain-of-function and loss-of-function studies demonstrated that the elevated HGF level induced by HFD have protective role against obesity and insulin resistance.

• cell proliferation
• chitosan
• deacetylation
• growth factor
• platelet activation
• platelet-rich plasma

• hepatic progenitor cells
• hepatic stellate cells
• macrophages

• Apoptosis
• High-mobility group box 1
• Migration
• Monocytes
• Platelets

• Animals
• Apoptosis/immunology
• Cell Movement/immunology
• Cells, Cultured
• HMGB1 Protein/immunology
• Inflammation/immunology
• Inflammation/pathology
• MAP Kinase Signaling System/immunology
• Mice
• Mice, Transgenic
• Monocytes/cytology
• Monocytes/immunology
• Monocytes/pathology
• Receptor for Advanced Glycation End Products/immunology
• Toll-Like Receptor 4/immunology

• D43 TW007560 FIC NIH HHS
• P50 GM053789 NIGMS NIH HHS
• R01 GM044100 NIGMS NIH HHS
• R35 GM119526 NIGMS NIH HHS

MicroRNA-122 (miR-122) is implicated as a regulator of physiological and pathophysiological processes in the liver. Overexpression of Gα₁₂ is associated with overall survival in patients with hepatocellular carcinoma (HCC). Array-based miRNA profiling was performed on Huh7 stably transfected with activated Gα₁₂ to find miRNAs regulated by the Gα₁₂ pathway; among them, miR-122 was most greatly repressed. miR-122 directly inhibits c-Met expression, playing a role in HCC progression. Gα₁₂ destabilized HNF4α by accelerating ubiquitination, impeding constitutive expression of miR-122. miR-122 mimic transfection diminished the ability of Gα₁₂ to increase c-Met and to activate ERK, STAT3, and Akt/mTOR, suppressing cell proliferation with augmented apoptosis. Consistently, miR-122 transfection prohibited tumor cell colony formation and endothelial tube formation. In a xenograft model, Gα₁₂ knockdown attenuated c-Met expression by restoring HNF4α levels, and elicited tumor cell apoptosis but diminished Ki67 intensities. In human HCC samples, Gα₁₂ levels correlated to c-Met and were inversely associated with miR-122. Both miR-122 and c-Met expression significantly changed in tumor node metastasis (TNM) stage II/III tumors. Moreover, changes in Gα₁₂ and miR-122 levels discriminated recurrence-free and overall survival rates of HCC patients. Collectively, Gα₁₂ overexpression in HCC inhibits MIR122 transactivation by inactivating HNF4α, which causes c-Met induction, contributing to cancer aggressiveness.

• G protein
• c-Met
• liver cancer
• non-coding RNA

• Hashimoto’s thyroiditis
• Nodular goiter
• hepatocyte growth factor
• hypothyroidism

• Adult
• Female
• Follow-Up Studies
• Goiter/blood
• Goiter/drug therapy
• Hashimoto Disease/blood
• Hashimoto Disease/drug therapy
• Hepatocyte Growth Factor/blood
• Humans
• Hypothyroidism/blood
• Hypothyroidism/drug therapy
• Thyroid Gland/diagnostic imaging
• Thyroxine/administration & dosage
• Thyroxine/pharmacology
• Treatment Outcome
• Young Adult

• CNS regeneration
• angiogenesis
• demyelination
• haemostasis
• inflammation
• neural stem/progenitor cells
• stroke

• TGF-β1
• adenomyosis
• epithelial–mesenchymal transition
• fibroblast-to-myofibroblast transdifferentiation
• fibrosis
• mouse
• platelet

Dysregulation of the PI3K/AKT/mammalian target of rapamycin (mTOR) pathway could contribute to the pathogenesis of autism spectrum disorders. In this study, phosphorylated Akt concentration was measured in 37 autistic children and 12, gender and age similar neurotypical, controls using an enzyme-linked immunosorbent assay. Akt levels were compared to biomarkers known to be associated with epidermal growth factor receptor (EGFR) and c-Met (hepatocyte growth factor (HGF) receptor) pathways and severity levels of 19 autism-related symptoms. We found phosphorylated Akt levels significantly lower in autistic children and low Akt levels correlated with high EGFR and HGF and low gamma-aminobutyric acid, but not other biomarkers. Low Akt levels also correlated significantly with increased severity of receptive language, conversational language, hypotonia, rocking and pacing, and stimming, These results suggest a relationship between decreased phosphorylated Akt and selected symptom severity in autistic children and support the suggestion that the AKT pathways may be associated with the etiology of autism.

• Akt
• EGF
• EGFR
• HGF
• autism
• symptom severity

Dentate neural stem cells produce neurons throughout life in mammals. Sonic hedgehog (Shh) is critical for maintenance of these cells; however, the perinatal source of Shh is enigmatic. In the present study, we examined the role of Shh expressed by hair follicles (HFs) that expand perinatally in temporal concordance with the proliferation of Shh-responding dentate stem cells. Specific inhibition of Shh from HFs or from epithelial sources in general hindered development of Shh-responding dentate stem cells. We also found that the blood–brain barrier (BBB) of the perinatal dentate gyrus (DG) is leaky with stem cells in the dentate exposed to blood-born factors. In attempting to identify how Shh might be transported in blood, we found that platelets contain epithelial Shh, provide Shh to the perinatal DG and that inhibition of platelet generation reduced hedgehog-responsive dentate stem cells.

DOI:http://dx.doi.org/10.7554/eLife.07834.001

Although most of the neurons in the brain have been made by the time we are born, new neurons develop throughout life in part of the brain called the hippocampus. These neurons are thought to help with learning and forming memories. Conditions such as depression and Alzheimer's disease have been linked to not being able to produce enough new neurons.

The neurons develop from a pool of stem cells in part of the hippocampus. A protein called Sonic Hedgehog (Shh) helps to ensure there are enough stem cells and control when they develop into new neurons. The brain cells that produce Shh in adult mice do not appear until a week after birth, by which point the stem cells are already present and generating neurons. This has led scientists to question where these cells get Shh from around the time of birth.

One idea is that cells outside of the brain contribute the Shh such as hair follicles—the structures that hairs grow out of—in the scalp. Hair follicles produce Shh, develop at around the same time as the brain stem cells, and are known to regulate the development of other nearby stem cells. So, Choe et al. conducted a series of experiments in genetically engineered newborn mice and found that the brain stem cells multiply at around the same time that the hair follicles start to produce Shh. Furthermore, reducing the amount of Shh produced by the hair follicles hampered the growth of these stem cells and caused fewer neurons to develop from the stem cell pool.

These results raised the question of how Shh gets from the hair follicles to the stem cell pool in the developing brain. In adult animals, a barrier exists between the brain and the blood supply to protect the brain from infection. However, parts of this barrier are still leaky before birth, which might allow blood cells to carry Shh to the brain. Cloe et al. found that platelets—the blood cells responsible for clotting—are able to carry Shh to the brain stem cell pool. Further experiments showed that preventing platelets from forming caused fewer stem cells to develop.

The suggestion that Shh from the epithelium—the tissue layer that hair follicles are found in—is able to signal to the brain during a specific window of time raises several questions that require further study. Does epithelial Shh also signal to other organs during embryonic or postnatal development? Does injury to the nervous system that increases the permeability of the blood–brain barrier lead to the delivery of Shh to the brain via the circulation in adult animals?

DOI:http://dx.doi.org/10.7554/eLife.07834.002

• Shh
• dentate gyrus
• developmental biology
• mouse
• neurogenesis
• neuroscience
• platelet
• stem cells