Sox9 regulates cell proliferation and is required for Paneth cell differentiation in the intestinal epithelium

Abstract

The HMG-box transcription factor Sox9 is expressed in the intestinal epithelium, specifically, in stem/progenitor cells and in Paneth cells. Sox9 expression requires an active β-catenin–Tcf complex, the transcriptional effector of the Wnt pathway. This pathway is critical for numerous aspects of the intestinal epithelium physiopathology, but processes that specify the cell response to such multipotential signals still remain to be identified. We inactivated the Sox9 gene in the intestinal epithelium to analyze its physiological function. Sox9 inactivation affected differentiation throughout the intestinal epithelium, with a disappearance of Paneth cells and a decrease of the goblet cell lineage. Additionally, the morphology of the colon epithelium was severely altered. We detected general hyperplasia and local crypt dysplasia in the intestine, and Wnt pathway target genes were up-regulated. These results highlight the central position of Sox9 as both a transcriptional target and a regulator of the Wnt pathway in the regulation of intestinal epithelium homeostasis.

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Affiliated Institutions

• University of Freiburg DE
• Centre National de la Recherche Scientifique FR
• Laboratoire d'Aérologie FR
• Inserm FR
• Institut Curie FR
• Gefluc Languedoc Roussillon FR
• Université de Montpellier FR
• Service de la Santé Publique CH
• Institut de Génomique Fonctionnelle FR
• Centre Hospitalier Universitaire de Nîmes FR

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