ArticleDiabetes2014
Pak3 promotes cell cycle exit and differentiation of β-cells in the embryonic pancreas and is necessary to maintain glucose homeostasis in adult mice.
Article in Diabetes, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 54 citations in OpenAlex.
- PAX gene expression in autosomal dominant polycystic kidney disease contributes to cyst expansion and regulates a gene network associated with cyst growth.Human molecular genetics · 2026Article
- Naphthoquinones mediate differentiation of human umbilical cord derived mesenchymal stem cells into insulin producing cells through regulation of Wnt and BMP pathways.BioImpacts : BI · 2026Article
- Comprehensive Characterization of Bihormonal Cells and Endocrine Cell Lineages in Mammalian Pancreatic Islets.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- ACSS2 mediates an epigenetic pathway to regulate β-cell adaptation during gestation in mice.Nature communications · 2025Article
- Review
- Extracellular matrix proteins refine microenvironments for pancreatic organogenesis from induced pluripotent stem cell differentiation.Theranostics · 2025Article
- Article
- Identification and characterization of intermediate states in mammalian neural crest cell epithelial to mesenchymal transition and delamination.bioRxiv : the preprint server for biology · 2024Article
- ETV5 regulates proliferation and cell cycle genes in the INS-1 (832/13) cell line independently of the concentration of secreted insulin.FEBS open bio · 2023Article
- Nutrient regulation of the islet epigenome controls adaptive insulin secretion.The Journal of clinical investigation · 2023Article
- The molecular basis of p21-activated kinase-associated neurodevelopmental disorders: From genotype to phenotype.Frontiers in neuroscience · 2023Review
- Three-Dimensional Microtumor Formation of Infantile Hemangioma-Derived Endothelial Cells for Mechanistic Exploration and Drug Screening.Pharmaceuticals (Basel, Switzerland) · 2022Article
- PAK3 is a key signature gene of the glioma proneural subtype and affects its proliferation, differentiation and growth.Cellular oncology (Dordrecht, Netherlands) · 2021Article
- The Essential Role of Stathmin in Myoblast C2C12 for Vertical Vibration-Induced Myotube Formation.Biomolecules · 2021Article
- Characterizing pancreatic β-cell heterogeneity in the streptozotocin model by single-cell transcriptomic analysis.Molecular metabolism · 2020Article
- A Network of microRNAs Acts to Promote Cell Cycle Exit and Differentiation of Human Pancreatic Endocrine Cells.iScience · 2019Article
- β-Cell Maturation and Identity in Health and Disease.International journal of molecular sciences · 2019Review
- Defining multistep cell fate decision pathways during pancreatic development at single-cell resolution.The EMBO journal · 2019Article
- Single-cell transcriptomic analyses reveal distinct dorsal/ventral pancreatic programs.EMBO reports · 2018Article
- Single-cell Transcriptomic Analyses of Mouse Pancreatic Endocrine Cells.Journal of visualized experiments : JoVE · 2018Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
The transcription factor neurogenin3 (Ngn3) triggers islet cell differentiation in the developing pancreas. However, little is known about the molecular mechanisms coupling cell cycle exit and differentiation in Ngn3(+) islet progenitors. We identified a novel effector of Ngn3 endocrinogenic function, the p21 protein-activated kinase Pak3, known to control neuronal differentiation and implicated in X-linked intellectual disability in humans. We show that Pak3 expression is initiated in Ngn3(+) endocrine progenitor cells and next maintained in maturing hormone-expressing cells during pancreas development as well as in adult islet cells. In Pak3-deficient embryos, the proliferation of Ngn3(+) progenitors and β-cells is transiently increased concomitantly with an upregulation of Ccnd1. β-Cell differentiation is impaired at E15.5 but resumes at later stages. Pak3-deficient mice do not develop overt diabetes but are glucose intolerant under high-fat diet (HFD). In the intestine, Pak3 is expressed in enteroendocrine cells but is not necessary for their differentiation. Our results indicate that Pak3 is a novel regulator of β-cell differentiation and function. Pak3 acts downstream of Ngn3 to promote cell cycle exit and differentiation in the embryo by a mechanism that might involve repression of Ccnd1. In the adult, Pak3 is required for the proper control of glucose homeostasis under challenging HFD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.