ArticleGastroenterology2009
Foxa1 and Foxa2 control the differentiation of goblet and enteroendocrine L- and D-cells in mice.
Article in Gastroenterology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
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Who cites it
94 citing papers in PubMed, 171 citations in OpenAlex.
- Type 2 diabetes is associated with impaired jejunal enteroendocrine GLP-1 cell lineage in human obesity.International journal of obesity (2005) · 2021Trial
- IL-22 increases proglucagon-expressing enteroendocrine cells via STAT3 in human iPSC-derived intestinal epithelium.Endocrinology · 2026Article
- Mettl14-mediated mJournal of endocrinological investigation · 2026Article
- Article
- Pioneer transcription factors direct tissue-specific cohesin chromatin entry and three-dimensional genome organization.Nature genetics · 2026Article
- FOXA2 in islet biology: Orchestrating pancreatic development and glucose homeostasis.Genes & diseases · 2026Review
- Emerging Role of Taste Receptors, Entero-Endocrine Cells in Type 2 Diabetes and Metabolic Disorders.Nutrients · 2026Review
- Single-nucleus multi-omics analysis of mouse small-intestinal Lgr5+ cell populations reveals Foxa3-induced Paneth cell-lineage differentiation.Communications biology · 2026Article
- Unraveling enteroendocrine cell lineage dynamics and associated gene regulatory networks during intestinal development.Biology open · 2025Article
- Enteroendocrine cell differentiation: Implications for human disease.Molecular and cellular endocrinology · 2025Review
- FOXA1 expression and its association with mucin expression and KRAS mutation in ovarian mucinous tumors: implications for tumor progression and differentiation.Virchows Archiv : an international journal of pathology · 2025Article
- Transcriptomic Landscape of Colorectal Mucinous Adenocarcinoma has Similarity with Intestinal Goblet Cell Differentiation.Current genomics · 2025Article
- The evolutionarily ancient FOXA transcription factors shape the murine gut microbiome via control of epithelial glycosylation.Developmental cell · 2024Article
- Salivary Gland Tissue Recombination Can Modify Cell Fate.Journal of dental research · 2024Article
- Comparative proteomics analysis of the mouse mini-gut organoid: insights into markers of gluten challenge from celiac disease intestinal biopsies.Frontiers in molecular biosciences · 2024Article
- Transcriptional Control: A Directional Sign at the Crossroads of Adult Hepatic Progenitor Cells' Fates.International journal of biological sciences · 2024Review
- The Assessment ofActa medica Lituanic · 2024Article
- Intertumoral lineage diversity and immunosuppressive transcriptional programs in well-differentiated gastroenteropancreatic neuroendocrine tumors.Science advances · 2023Article
- High FOXA1 levels induce ER transcriptional reprogramming, a pro-metastatic secretome, and metastasis in endocrine-resistant breast cancer.Cell reports · 2023Article
- Comprehensive analyses of partially methylated domains and differentially methylated regions in esophageal cancer reveal both cell-type- and cancer-specific epigenetic regulation.Genome biology · 2023Article
34 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND &
aimsThe winged helix transcription factors Foxa1 and Foxa2 are expressed in all epithelia of the gastrointestinal tract from its embryonic origin into adulthood. In vitro studies have shown that Foxa1/a2 can transactivate the promoters of Mucin 2 (Muc2), which is expressed in goblet cells, and of preproglucagon, which is expressed in enteroendocrine cells. These findings suggest Foxa1/a2 as critical factors in the differentiation of gut epithelial cells.
methodsMice with intestine-specific simultaneous deletion of Foxa1 and Foxa2 were derived using the Cre-loxP system and analyzed using histologic and molecular means.
resultsBoth Foxa1 and Foxa2 were deleted successfully in the epithelia of the small intestine and colon using Villin-Cre mice. Immunohistochemical staining showed that Foxa1/a2 mutants lack glucagon-like peptide-1- and peptide-2-expressing cells (L-cells), and have reduced numbers of somatostatin (D-cells) and peptide YY-expressing cells (L-cells). Preproglucagon, somatostatin, and peptide YY messenger RNA (mRNA) levels also were reduced significantly in Foxa1/a2 mutants. Thus, Foxa1 and Foxa2 are essential regulators of these enteroendocrine lineages in vivo. The mRNA levels of transcription factors Islet-1 and Pax6 were reduced significantly in the small intestine, showing that Foxa1 and Foxa2 impact on a transcription factor network in the enteroendocrine lineage. In addition, deletion of Foxa1/a2 caused a reduction in goblet cell number with altered expression of the secretory mucins Muc2, Mucin5b, Mucin5ac, and Mucin 6.
conclusionsThe winged helix factors Foxa1 and Foxa2 are essential members of the transcription factor network that govern secretory cell differentiation in the mammalian gastrointestinal tract.
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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.