ArticleDevelopment (Cambridge, England)2015
Hnf1b controls pancreas morphogenesis and the generation of Ngn3+ endocrine progenitors.
Article in Development (Cambridge, England), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 125 citations in OpenAlex.
- E12.5 pancreatic bud-derived cells are detected in recipient pancreata after intraplacental transplantation, but Pdx1-deficient recipients lack a macroscopically detectable pancreas.Scientific reports · 2026Article
- Review
- SOX9: dosage- and context-dependent functions in pancreatic development and β-cell biology.Cell communication and signaling : CCS · 2026Review
- BARTsc identifies key transcriptional regulators from single-cell omics data.bioRxiv : the preprint server for biology · 2026Article
- Systemic control of HNF1B-driven redox homeostasis by N6-adenosine methylation.Nucleic acids research · 2026Article
- Hepatic dysfunction, hyperuricemia, and multiple renal cysts in adolescence: A case report with HNF1B deficiency and literature review.Clinical nephrology. Case studies · 2026Article
- Fetal Pancreas in Growth Restriction: A Prenatal Window Into Metabolic and Genetic Risk.Prenatal diagnosis · 2025Article
- Bridging pancreatic and hepatic development: overlapping genes and their role in diabetes.Cellular & molecular biology letters · 2025Review
- MODY5 and 17q12 Microdeletion Syndrome: Phenotype Variability, Prenatal and Postnatal Counseling.Genes · 2025Review
- Why all MODY variants in transcription factor genes are dominantly inherited.Frontiers in genetics · 2025Article
- Identification of mouse and human embryonic pancreatic cells with adult ProcrFrontiers in endocrinology · 2025Article
- Review
- The SWI/SNF chromatin remodelling complex regulates pancreatic endocrine cell expansion and differentiation in mice in vivo.Diabetologia · 2024Article
- RFX6 haploinsufficiency predisposes to diabetes through impaired beta cell function.Diabetologia · 2024Article
- Development of the Pancreatic Ducts and Their Contribution to Organogenesis.Advances in anatomy, embryology, and cell biology · 2024Review
- The role of noncoding RNAs in pancreatic birth defects.Birth defects research · 2023Review
- Genetic and Clinical Characterization of Patients with HNF1B-Related MODY in Croatia.Journal of personalized medicine · 2023Article
- Acinar-to-Ductal Metaplasia (ADM): On the Road to Pancreatic Intraepithelial Neoplasia (PanIN) and Pancreatic Cancer.International journal of molecular sciences · 2023Review
- iPSC-Derived Pancreatic Progenitors Lacking FOXA2 Reveal Alterations in miRNA Expression Targeting Key Pancreatic Genes.Stem cell reviews and reports · 2023Article
- MafB-dependent neurotransmitter signaling promotes β cell migration in the developing pancreas.Development (Cambridge, England) · 2023Article
18 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Heterozygous mutations in the human HNF1B gene are associated with maturity-onset diabetes of the young type 5 (MODY5) and pancreas hypoplasia. In mouse, Hnf1b heterozygous mutants do not exhibit any phenotype, whereas the homozygous deletion in the entire epiblast leads to pancreas agenesis associated with abnormal gut regionalization. Here, we examine the specific role of Hnf1b during pancreas development, using constitutive and inducible conditional inactivation approaches at key developmental stages. Hnf1b early deletion leads to a reduced pool of pancreatic multipotent progenitor cells (MPCs) due to decreased proliferation and increased apoptosis. Lack of Hnf1b either during the first or the secondary transitions is associated with cystic ducts. Ductal cells exhibit aberrant polarity and decreased expression of several cystic disease genes, some of which we identified as novel Hnf1b targets. Notably, we show that Glis3, a transcription factor involved in duct morphogenesis and endocrine cell development, is downstream Hnf1b. In addition, a loss and abnormal differentiation of acinar cells are observed. Strikingly, inactivation of Hnf1b at different time points results in the absence of Ngn3(+) endocrine precursors throughout embryogenesis. We further show that Hnf1b occupies novel Ngn3 putative regulatory sequences in vivo. Thus, Hnf1b plays a crucial role in the regulatory networks that control pancreatic MPC expansion, acinar cell identity, duct morphogenesis and generation of endocrine precursors. Our results uncover an unappreciated requirement of Hnf1b in endocrine cell specification and suggest a mechanistic explanation of diabetes onset in individuals with MODY5.
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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.