Dab1 and reelin participate in a common signal pathway that controls intestinal crypt/villus unit dynamics
Background information: The myofibroblasts placed underneath the epithelium of the rodent small intestine express reelin, and the reelin absence modifies both the morphology and the cell renewal processes of the crypt-villus unit. In the developing central nervous system, the reelin effects are medi...
| Autores: | , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión aceptada para publicación |
| Fecha de publicación: | 2014 |
| País: | España |
| Institución: | Universidad de Sevilla (US) |
| Repositorio: | idUS. Depósito de Investigación de la Universidad de Sevilla |
| OAI Identifier: | oai:idus.us.es:11441/152072 |
| Acceso en línea: | https://hdl.handle.net/11441/152072 https://doi.org/10.1111/boc.201300078 |
| Access Level: | acceso abierto |
| Palabra clave: | Dab1 Epithelium Intestine Reelin |
| Sumario: | Background information: The myofibroblasts placed underneath the epithelium of the rodent small intestine express reelin, and the reelin absence modifies both the morphology and the cell renewal processes of the crypt-villus unit. In the developing central nervous system, the reelin effects are mediated by the disabled-1 (Dab1) protein. The present work explores whether Dab1 mediates the reelin control of the crypt-villus unit dynamics by examining in the mouse small intestine the consequences of the absence of (i) Dab1 (scrambler mutation) on crypt-villus unit cell renewal processes and morphology and (ii) reelin (reeler mutation) on the intestinal expression of Dab1. Results: The effects of the scrambler mutation on the crypt-villus unit renewal processes are remarkably similar to those caused by the lack of reelin. Thus, both mutations significantly reduce epithelial cell proliferation, migration and apoptosis, and the number of Paneth cells; affect the morphology of the villus, and expand the intercellular space of the adherens junctions and desmosomes. The Western blot assays reveal that the Dab1 isoform present in the enterocytes has a molecular weight of ∼63 kDa and that in the brain of ∼82 kDa. They also reveal that the absence of reelin increases Dab1 abundance in both brain and enterocytes. Conclusions: All together, the current findings link reelin with Dab1 and suggest that Dab1 functions downstream of reelin action on the homeostasis of the crypt-villus unit. |
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