Mammalian Intestinal Development and Differentiation—The State of the ArtSummary
The development of the mammalian intestine, from its earliest origins as a morphologically uniform sheet of endoderm cells during gastrulation into the complex organ system that is essential for the life of the organism, is a truly fascinating process. During midgestation development, reciprocal int...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Cellular and Molecular Gastroenterology and Hepatology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352345X23001406 |
| _version_ | 1797676629602861056 |
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| author | Hannah M. Kolev Klaus H. Kaestner |
| author_facet | Hannah M. Kolev Klaus H. Kaestner |
| author_sort | Hannah M. Kolev |
| collection | DOAJ |
| description | The development of the mammalian intestine, from its earliest origins as a morphologically uniform sheet of endoderm cells during gastrulation into the complex organ system that is essential for the life of the organism, is a truly fascinating process. During midgestation development, reciprocal interactions between endoderm-derived epithelium and mesoderm-derived mesenchyme enable villification, or the conversion of a radially symmetric pseudostratified epithelium into the functional subdivision of crypts and villi. Once a mature crypt–villus axis is established, proliferation and differentiation of new epithelial cells continue throughout life. Spatially localized signals including the wingless and Int-1, fibroblast growth factor, and Hippo systems, among others, ensure that new cells are being born continuously in the crypt. As cells exit the crypt compartment, a gradient of bone morphogenetic protein signaling limits proliferation to allow for the specification of multiple mature cell types. The first major differentiation decision is dependent on Notch signaling, which specifies epithelial cells into absorptive and secretory lineages. The secretory lineage is subdivided further into Paneth, goblet, tuft, and enteroendocrine cells via a complex network of transcription factors. Although some of the signaling molecules are produced by epithelial cells, critical components are derived from specialized crypt-adjacent mesenchymal cells termed telocytes, which are marked by Forkhead box l1, GLI Family Zinc Finger 1, and platelet-derived growth factor receptor α. The crucial nature of these processes is evidenced by the multitude of intestinal disorders such as colorectal cancer, short-bowel syndrome, and inflammatory bowel disease, which all reflect perturbations of the development and/or differentiation of the intestine. |
| first_indexed | 2024-03-11T22:32:00Z |
| format | Article |
| id | doaj.art-8a5c13747fe54ea6b79123fc6cd1c659 |
| institution | Directory Open Access Journal |
| issn | 2352-345X |
| language | English |
| last_indexed | 2024-03-11T22:32:00Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cellular and Molecular Gastroenterology and Hepatology |
| spelling | doaj.art-8a5c13747fe54ea6b79123fc6cd1c6592023-09-23T05:11:16ZengElsevierCellular and Molecular Gastroenterology and Hepatology2352-345X2023-01-01165809821Mammalian Intestinal Development and Differentiation—The State of the ArtSummaryHannah M. Kolev0Klaus H. Kaestner1Department of Genetics and Center for Molecular Studies in Digestive and Liver Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PennsylvaniaCorrespondence Address correspondence to: Klaus H. Kaestner, PhD, MS, Department of Genetics and Center for Molecular Studies in Digestive and Liver Diseases, Perelman School of Medicine, University of Pennsylvania, 12-126 Translational Research Center, 3400 Civic Center Boulevard, Philadelphia, Pennsylvania 19104-6145.; Department of Genetics and Center for Molecular Studies in Digestive and Liver Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PennsylvaniaThe development of the mammalian intestine, from its earliest origins as a morphologically uniform sheet of endoderm cells during gastrulation into the complex organ system that is essential for the life of the organism, is a truly fascinating process. During midgestation development, reciprocal interactions between endoderm-derived epithelium and mesoderm-derived mesenchyme enable villification, or the conversion of a radially symmetric pseudostratified epithelium into the functional subdivision of crypts and villi. Once a mature crypt–villus axis is established, proliferation and differentiation of new epithelial cells continue throughout life. Spatially localized signals including the wingless and Int-1, fibroblast growth factor, and Hippo systems, among others, ensure that new cells are being born continuously in the crypt. As cells exit the crypt compartment, a gradient of bone morphogenetic protein signaling limits proliferation to allow for the specification of multiple mature cell types. The first major differentiation decision is dependent on Notch signaling, which specifies epithelial cells into absorptive and secretory lineages. The secretory lineage is subdivided further into Paneth, goblet, tuft, and enteroendocrine cells via a complex network of transcription factors. Although some of the signaling molecules are produced by epithelial cells, critical components are derived from specialized crypt-adjacent mesenchymal cells termed telocytes, which are marked by Forkhead box l1, GLI Family Zinc Finger 1, and platelet-derived growth factor receptor α. The crucial nature of these processes is evidenced by the multitude of intestinal disorders such as colorectal cancer, short-bowel syndrome, and inflammatory bowel disease, which all reflect perturbations of the development and/or differentiation of the intestine.http://www.sciencedirect.com/science/article/pii/S2352345X23001406intestinal developmentstem cellsstem cell nichetelocytes |
| spellingShingle | Hannah M. Kolev Klaus H. Kaestner Mammalian Intestinal Development and Differentiation—The State of the ArtSummary Cellular and Molecular Gastroenterology and Hepatology intestinal development stem cells stem cell niche telocytes |
| title | Mammalian Intestinal Development and Differentiation—The State of the ArtSummary |
| title_full | Mammalian Intestinal Development and Differentiation—The State of the ArtSummary |
| title_fullStr | Mammalian Intestinal Development and Differentiation—The State of the ArtSummary |
| title_full_unstemmed | Mammalian Intestinal Development and Differentiation—The State of the ArtSummary |
| title_short | Mammalian Intestinal Development and Differentiation—The State of the ArtSummary |
| title_sort | mammalian intestinal development and differentiation the state of the artsummary |
| topic | intestinal development stem cells stem cell niche telocytes |
| url | http://www.sciencedirect.com/science/article/pii/S2352345X23001406 |
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