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

Philippe Blache (1) , Marc van de Wetering (2) , Isabelle Duluc (3) , Claire Domon (3) , Philippe Berta (1) , Jean-Noël Freund (3) , Hans Clevers (2) , Philippe Jay (1)

1 IGH - Institut de génétique humaine
2 Hubrecht Laboratory
3 Ontogénèse et pathologie du système digestif : rôle du microenvironnement cellulaire et moléculaire

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 beta-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.

Mots clés: SOX9; WNT; CDX2; MUC2; intestinal epithelium; stem cells; differentiation

Domaines: Cancer; Génétique; Médecine humaine et pathologie

Philippe Blache, Marc van de Wetering, Isabelle Duluc, Claire Domon, Philippe Berta, et al.. SOX9 is an intestine crypt transcription factor, is regulated by the Wnt pathway, and represses the CDX2 and MUC2 genes.. Journal of Cell Biology, 2004, 166 (1), pp.37-47. ⟨10.1083/jcb.200311021⟩. ⟨hal-00266987⟩