| First Author | Jedlicka P | Year | 2009 |
| Journal | Am J Pathol | Volume | 174 |
| Issue | 4 | Pages | 1280-90 |
| PubMed ID | 19264912 | Mgi Jnum | J:147085 |
| Mgi Id | MGI:3839205 | Doi | 10.2353/ajpath.2009.080409 |
| Citation | Jedlicka P, et al. (2009) Ets transcription factors control epithelial maturation and transit and crypt-villus morphogenesis in the mammalian intestine. Am J Pathol 174(4):1280-90 |
| abstractText | Members of the Ets transcription factor family are widely expressed in both the developing and mature mammalian intestine, but their biological functions remain primarily uncharacterized. We used a dominant repressor transgene approach to probe the function of epithelial Ets factors in the homeostasis of the crypt-villus unit, the functional unit of the small intestine. We show that targeted expression in small intestinal epithelium of a fusion protein composed of the Engrailed repressor domain and the Erm DNA-binding domain (En/Erm) results in marked disruption of normal crypt-villus homeostasis, including a cell-autonomous disturbance of epithelial maturation, increased epithelial transit, severe villus dysmorphogenesis, and crypt dysmorphogenesis. The epithelial maturation disturbance is independent of the regulation of TGFbetaRII levels, in contrast to Ets-mediated epithelial differentiation during development; rather, regulation of Cdx2 expression may play a role. The villus dysmorphogenesis is independent of alterations in the crypt-villus boundary and inappropriate beta-catenin activation, and thus appears to represent a new mechanism controlling villus architectural organization. An Analysis of animals mosaic for En/Erm expression suggests that crypt nonautonomous mechanisms underlie the crypt dysmorphogenesis phenotype. Our studies thus uncover novel Ets-regulated pathways of intestinal homeostasis in vivo. Interestingly, the overall En/Erm phenotype of disturbed crypt-villus homeostasis is consistent with recently identified Ets function(s) in the restriction of intestinal epithelial tumorigenesis. |
