Sox9 regulates cell proliferation and is required for Paneth cell differentiation in the intestinal epithelium.
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 beta-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.
Bastide
Pauline
P
INSERM U661, Department of Cellular and Molecular Oncology, Centre National de la Recherche Scientifique UMR5203, Université de Montpellier I and Service d'Anatomie-Pathologie, Centre Hospitalier Universitaire Carémeau, Nimes, France.
Darido
Charbel
C
Pannequin
Julie
J
Kist
Ralf
R
Robine
Sylvie
S
Marty-Double
Christiane
C
Bibeau
Frédéric
F
Scherer
Gerd
G
Joubert
Dominique
D
Hollande
Frédéric
F
Blache
Philippe
P
Jay
Philippe
P
D000818:Animals; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003106:Colon / Q000166:cytology / Q000378:metabolism*; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D019879:Paneth Cells / Q000166:cytology / Q000378:metabolism*; D055758:SOX9 Transcription Factor; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D006609:High Mobility Group Proteins; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; C527933:Sox9 protein, mouse; D014157:Transcription Factors
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