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PMID: 17698607 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The Journal of cell biology ·Vol. 178 ·No. 4 ·2007-08-13 ·Pages 635-48

Bastide P, Darido C, Pannequin J, Kist R, Robine S, Marty-Double C, Bibeau F, Scherer G, Joubert D, Hollande F, Blache P, Jay P

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 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.

MeSH Terms
Animals Cell Differentiation Cell Line, Tumor Cell Proliferation Colon/cytology,metabolism High Mobility Group Proteins/genetics,metabolism Humans Mice Mice, Inbred C57BL Paneth Cells/cytology,metabolism SOX9 Transcription Factor Transcription Factors/genetics,metabolism
Chemicals
High Mobility Group Proteins SOX9 Transcription Factor SOX9 protein, human Sox9 protein, mouse Transcription Factors
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Bastide Pauline
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
Pannequin Julie
Kist Ralf
Robine Sylvie
Marty-Double Christiane
Bibeau Frédéric
Scherer Gerd
Joubert Dominique
Hollande Frédéric
Blache Philippe
Jay Philippe
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200704152
Published
2007-08-13
Pages
635-48
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2064470
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.200704152 PMC Full Text View journal details
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