Unknown

Dataset Information

0

Ets transcription factors control epithelial maturation and transit and crypt-villus morphogenesis in the mammalian intestine.


ABSTRACT: 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.

SUBMITTER: Jedlicka P 

PROVIDER: S-EPMC2671360 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

altmetric image

Publications

Ets transcription factors control epithelial maturation and transit and crypt-villus morphogenesis in the mammalian intestine.

Jedlicka Paul P   Sui Xiaomei X   Sussel Lori L   Gutierrez-Hartmann Arthur A  

The American journal of pathology 20090305 4


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  ...[more]

Similar Datasets

| S-EPMC4997266 | biostudies-literature
| S-EPMC8883354 | biostudies-literature
| S-EPMC1145182 | biostudies-literature
| S-EPMC6625996 | biostudies-literature
| S-EPMC3530936 | biostudies-literature
2006-12-08 | GSE6443 | GEO
2014-01-06 | GSE51398 | GEO
| S-EPMC9858500 | biostudies-literature
2014-01-06 | E-GEOD-51398 | biostudies-arrayexpress
| S-EPMC3114882 | biostudies-literature