ArticleGenes & development2008
Dynamic regulation of Pdx1 enhancers by Foxa1 and Foxa2 is essential for pancreas development.
Article in Genes & development, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 192 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
192 citing papers in PubMed, 307 citations in OpenAlex.
- Resolving human α versus β cell fate allocation for the generation of stem cell-derived islets.Nature communications · 2026Article
- FOXA2 in islet biology: Orchestrating pancreatic development and glucose homeostasis.Genes & diseases · 2026Review
- Brown Seaweeds and Their Bioactive Compounds in Type 2 Diabetes: Mechanisms Underlying Metabolic Regulation.International journal of molecular sciences · 2026Review
- Article
- FOXA2 in cancer: from fundamental biology to clinical translation.Frontiers in oncology · 2026Review
- MicroRNA 375 and diabetes: A key regulator of β cell function and a promising non-invasive biomarker.World journal of diabetes · 2025Review
- Bridging pancreatic and hepatic development: overlapping genes and their role in diabetes.Cellular & molecular biology letters · 2025Review
- STAT3 sustains tumorigenicity following mutant KRAS ablation.EMBO reports · 2025Article
- The key regulation of LncRNA MALAT during reprogramming of primary mouse hepatocytes into insulin producing cells.Scientific reports · 2025Article
- FOXM1 cooperates with ERα to regulate functional β-cell mass.American journal of physiology. Endocrinology and metabolism · 2025Article
- Enhancer reprogramming: critical roles in cancer and promising therapeutic strategies.Cell death discovery · 2025Review
- FoxA1/2-dependent epigenomic reprogramming drives lineage switching in lung adenocarcinoma.Developmental cell · 2025Article
- A framework to mine laser microdissection-based omics data and uncover regulators of pancreatic cancer heterogeneity.GigaScience · 2025Article
- MODY PDX1Frontiers in endocrinology · 2025Article
- Post translational modification regulation of transcription factors governing pancreatic β-cell identity and functional mass.Frontiers in endocrinology · 2025Review
- Foxa deficiency restricts hepatitis B virus biosynthesis through epigenic silencing.Journal of virology · 2024Article
- Heterogeneous enhancer states orchestrate β cell responses to metabolic stress.Nature communications · 2024Article
- The evolutionarily ancient FOXA transcription factors shape the murine gut microbiome via control of epithelial glycosylation.Developmental cell · 2024Article
- FOXA1 and FOXA2: the regulatory mechanisms and therapeutic implications in cancer.Cell death discovery · 2024Review
- Solid pseudopapillary neoplasm (SPN) of the pancreas: current understanding on its malignant potential and management.Discover oncology · 2024Review
132 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The onset of pancreas development in the foregut endoderm is marked by activation of the homeobox gene Pdx1 (IPF1). Pdx1 is essential for the expansion of the pancreatic primordium and the development of endocrine islets. The control of Pdx1 expression has been only partially elucidated. We demonstrate here that the winged-helix transcription factors Foxa1 and Foxa2 co-occupy multiple regulatory domains in the Pdx1 gene. Compound conditional ablation of both Foxa1 and Foxa2 in the pancreatic primordium results in complete loss of Pdx1 expression and severe pancreatic hypoplasia. Mutant mice exhibit hyperglycemia with severely disrupted acinar and islet development, and die shortly after birth. Assessment of developmental markers in the mutant pancreas revealed a failure in the expansion of the pancreatic anlage, a blockage of exocrine and endocrine cell differentiation, and an arrest at the primitive duct stage. Comparing their relative developmental activity, we find that Foxa2 is the major regulator in promoting pancreas development and cell differentiation. Using chromatin immunoprecipitations (ChIP) and ChIP sequencing (ChIPSeq) of fetal pancreas and islet chromatin, we demonstrate that Foxa1 and Foxa2 predominantly occupy a distal enhancer at -6.4 kb relative to the transcriptional start site in the Pdx1 gene. In addition, occupancy of the well-characterized proximal Pdx1 enhancer by Foxa1 and Foxa2 is developmental stage-dependent. Thus, the regulation of Pdx1 expression by Foxa1 and Foxa2 is a key early event controlling the expansion and differentiation of the pancreatic primordia.
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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.