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Published 5 July 2004. doi:10.1083/jcb.200311021
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 166, Number 1, 37-47
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Article

 SOX9 is an intestine crypt transcription factor, is regulated by the Wnt pathway, and represses the CDX2 and MUC2 genes

Philippe Blache1, Marc van de Wetering2, Isabelle Duluc3, Claire Domon3, Philippe Berta1, Jean-Noël Freund3, Hans Clevers2, and Philippe Jay1

1 Institut de Génétique Humaine, Centre National de la Recherche Scientifique (CNRS) UPR1142, 34396 Montpellier, Cedex 5, France
2 Hubrecht Laboratory, Centre for Biomedical Genetics, 3584 CT Utrecht, Netherlands
3 Institut National de la Santé et de la Recherche Médicale (INSERM) U381, F-67200 Strasbourg, France

Address correspondence to Philippe Jay, Institut de Génétique Humaine, CNRS UPR1142, 141 rue de la Cardonille, 34396 Montpellier, Cedex 5, France. Tel.: 33-499-61-99-40. Fax: 33-499-61-99-01. email: pj{at}igh.cnrs.fr


Abstract
TCF and SOX proteins belong to the high mobility group box transcription factor family. Whereas TCFs, the transcriptional effectors of the Wnt pathway, have been widely implicated in the development, homeostasis and disease of the intestine epithelium, little is known about the function of the SOX proteins in this tissue. Here, we identified SOX9 in a SOX expression screening in the mouse fetal intestine. We report that the SOX9 protein is expressed in the intestinal epithelium in a pattern characteristic of Wnt targets. We provide in vitro and in vivo evidence that a bipartite ß-catenin/TCF4 transcription factor, the effector of the Wnt signaling pathway, is required for SOX9 expression in epithelial cells. Finally, in colon epithelium-derived cells, SOX9 transcriptionally represses the CDX2 and MUC2 genes, normally expressed in the mature villus cells of the intestinal epithelium, and may therefore contribute to the Wnt-dependent maintenance of a progenitor cell phenotype.

Key Words: SOX9; Wnt; CDX2; intestinal epithelium; differentiation

The online version of this article contains supplemental material.

Abbreviations used in this paper: CD, campomelic dysplasia; cyt-E-cadherin, cytoplasmic domain of E-cadherin.


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