ArticleDevelopmental biology2016
Iterative use of nuclear receptor Nr5a2 regulates multiple stages of liver and pancreas development.
Article in Developmental biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 45 citations in OpenAlex.
- Comparative transcriptomics reveal the common anteroposterior molecular blueprint of adult bilaterian guts.PLoS biology · 2026Article
- Exploring the Expanding Role of Nuclear Receptor LRH-1/NR5A2 in Cell Biology and Immunity.International journal of cell biology · 2026Review
- An animal model recapitulates human hepatic diseases associated withProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Statistical modeling of immunoprecipitation efficiency of MeRIP-seq data enabled accurate detection and quantification of epitranscriptome.Computational and structural biotechnology journal · 2025Article
- CRISPR screening uncovers a long-range enhancer for ONECUT1 in pancreatic differentiation and links a diabetes risk variant.Cell reports · 2024Article
- Article
- Inhibiting NR5A2 targets stemness in pancreatic cancer by disrupting SOX2/MYC signaling and restoring chemosensitivity.Journal of experimental & clinical cancer research : CR · 2023Article
- Inferring regulators of cell identity in the human adult pancreas.NAR genomics and bioinformatics · 2023Article
- Single-Cell RNA Sequencing of Sox17-Expressing Lineages Reveals Distinct Gene Regulatory Networks and Dynamic Developmental Trajectories.Stem cells (Dayton, Ohio) · 2023Article
- Nuclear receptor Nr5a2 promotes diverse connective tissue fates in the jaw.Developmental cell · 2023Article
- Key transcriptional effectors of the pancreatic acinar phenotype and oncogenic transformation.PloS one · 2023Article
- Embryonic alcohol exposure disrupts the ubiquitin-proteasome system.JCI insight · 2022Article
- Nuclear receptor subfamily 5 group A member 2 (NR5A2): role in health and diseases.Molecular biology reports · 2021Review
- Global properties of regulatory sequences are predicted by transcription factor recognition mechanisms.Genome biology · 2021Article
- Fetal alcohol spectrum disorder predisposes to metabolic abnormalities in adulthood.The Journal of clinical investigation · 2020Article
- Development of the First Low Nanomolar Liver Receptor Homolog-1 Agonist through Structure-guided Design.Journal of medicinal chemistry · 2019Article
- Modelling human hepato-biliary-pancreatic organogenesis from the foregut-midgut boundary.Nature · 2019Article
- Regulation of the Pancreatic Exocrine Differentiation Program and Morphogenesis by Onecut 1/Hnf6.Cellular and molecular gastroenterology and hepatology · 2019Article
- Lower Nr5a2 Level Downregulates the β-Catenin and TCF-4 Expression in Caerulein-Induced Pancreatic Inflammation.Frontiers in physiology · 2019Article
- Liver receptor homolog-1 (NR5a2) regulates CD95/Fas ligand transcription and associated T-cell effector functions.Cell death & disease · 2017Article
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
Abstract
The stepwise progression of common endoderm progenitors into differentiated liver and pancreas organs is regulated by a dynamic array of signals that are not well understood. The nuclear receptor subfamily 5, group A, member 2 gene nr5a2, also known as Liver receptor homolog-1 (Lrh-1) is expressed in several tissues including the developing liver and pancreas. Here, we interrogate the role of Nr5a2 at multiple developmental stages using genetic and chemical approaches and uncover novel pleiotropic requirements during zebrafish liver and pancreas development. Zygotic loss of nr5a2 in a targeted genetic null mutant disrupted the development of the exocrine pancreas and liver, while leaving the endocrine pancreas intact. Loss of nr5a2 abrogated exocrine pancreas markers such as trypsin, while pancreas progenitors marked by ptf1a or pdx1 remained unaffected, suggesting a role for Nr5a2 in regulating pancreatic acinar cell differentiation. In the developing liver, Nr5a2 regulates hepatic progenitor outgrowth and differentiation, as nr5a2 mutants exhibited reduced hepatoblast markers hnf4α and prox1 as well as differentiated hepatocyte marker fabp10a. Through the first in vivo use of Nr5a2 chemical antagonist Cpd3, the iterative requirement for Nr5a2 for exocrine pancreas and liver differentiation was temporally elucidated: chemical inhibition of Nr5a2 function during hepatopancreas progenitor specification was sufficient to disrupt exocrine pancreas formation and enhance the size of the embryonic liver, suggesting that Nr5a2 regulates hepatic vs. pancreatic progenitor fate choice. Chemical inhibition of Nr5a2 at a later time during pancreas and liver differentiation was sufficient to block the formation of mature acinar cells and hepatocytes. These findings define critical iterative and pleiotropic roles for Nr5a2 at distinct stages of pancreas and liver organogenesis, and provide novel perspectives for interpreting the role of Nr5a2 in disease.
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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.