Minireview: Development and Differentiation of Gut Endocrine Cells
Abstract
For over 30 yr, it has been known that enteroendocrine cells derive from common precursor cells in the intestinal crypts. Until recently, relatively little was understood about the events that result in commitment to endocrine differentiation or the segregation of over 10 different hormone-expressing cell types in the gastrointestinal tract. The earliest cell fate decisions appear to be regulated by the Notch signaling pathway. Notch is inactive in endocrine precursor cells, allowing for expression of the proendocrine basic helix-loop-helix proteins Math1 and neurogenin3. Differentiating precursor cells activate Notch in neighboring cells to switch off expression of proendocrine factors and inhibit endocrine differentiation. Math1 is the first factor involved in endocrine specification, committing cells to become one of three secretory lineages-goblet, Paneth, and enteroendocrine. Neurogenin3 appears to be a downstream target that is essential for endocrine cell differentiation. Events that control the segregation of each mature lineage from progenitor cells have not been characterized in detail. The transcription factors Pax4, Pax6, BETA2/NeuroD, and pancreatic-duodenal homeobox 1 have all been implicated in enteroendocrine differentiation. BETA2/NeuroD appears to coordinate secretin gene expression in S-type enteroendocrine cells with cell cycle arrest as cells terminally differentiate. Powerful genetic approaches have established the murine intestine as the most important model for studying enteroendocrine differentiation. Enteroendocrine cells in the mouse are remarkably similar to those in humans, making it likely that insights learned from the mouse may contribute to both our understanding and treatment of a variety of human disorders.
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As afferent nerves are not exposed to the luminal side of the intestine, under normal circumstances sensory neurons are indirectly activated by stimuli in the intestinal lumen via paracrine signaling, which is mediated by compounds such as serotonin, cholecystokinin, histamine, secretin, somatostatin, melatonin, uroguanylin, and corticotrophin-releasing factor, all of which can be released from ne
“As afferent nerves are not exposed to the luminal side of the intestine, under normal circumstances sensory neurons are indirectly activated by stimuli in the intestinal lumen via paracrine signaling, which is mediated by compounds such as serotonin, cholecystokinin, histamine, secretin, somatostatin, melatonin, uroguanylin, and corticotrophin-releasing factor, all of which can be released from ne”
From Principles and clinical implications of the brain-gut-enteric microbiota axis (2009) · cites this paper as [68]
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- Authors
- Schonhoff, S. E., Giel-Moloney, M., & Leiter, A. B.
- Affiliations
- Tufts University (US)
- Division of Gastroenterology, GRASP Digestive Disease Center, Tufts-New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02111
- ORCID
- Leiter, Andrew B.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2004-06-01
- Volume
- 145
- Issue
- 6
- Pages
- 2639-2644
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2072287846
- Cited by
- 322
- References
- 59
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 6 · 2023: 6 · 2022: 5 · 2021: 7 · 2020: 19 · 2019: 15 · 2018: 15 · 2017: 21 · 2016: 17 · 2015: 19 · 2014: 22 · 2013: 17 · 2012: 18
- FWCI
- 1.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (T32 CA65441, T32CA065441)
- National Institute of Diabetes and Digestive and Kidney Diseases (T32 DK-07542, T32DK007542, R01DK052870, P30 DK-34928, P30DK034928, DK43673, R01DK043673, DK52870)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Digestive system and related health
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Keywords
- enteroendocrine cells, Notch signaling, Math1, neurogenin 3, goblet cells, Paneth cells, Pax4, Pax6, neurogenic differentiation, PDX1, secretin, cell cycle arrest, intestinal development
- MeSH terms
- Animals, Cell Differentiation, Endocrine Glands, Intestinal Mucosa, Membrane Proteins, Nerve Tissue Proteins, Transcription Factors, Signal Transduction, Cellular Senescence, Multipotent Stem Cells, Basic Helix-Loop-Helix Proteins, Receptors, Notch
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