SOX9 is required for the differentiation of paneth cells in the intestinal epithelium.
OBJECTIVE
The transcription factor SOX9 has been shown previously to have an essential role in the differentiation of a small number of discrete cell lineages. In the intestine, Sox9 is expressed in the epithelial cells of the crypts and is a target of Wnt signaling.


METHODS
To examine the function of SOX9 in the intestine, we inactivated the Sox9 gene in intestinal epithelial cells by generating mice that harbored a conditional Sox9 gene and a Villin-Cre transgene.


RESULTS
In the absence of SOX9, Paneth cells were not formed, but the differentiation of other intestinal epithelial cell types was unaffected. The lack of SOX9 also lead to crypt enlargement, to a marked increase in cell proliferation throughout the crypts, and to replacement of the Paneth cells by proliferating epithelial cells.


CONCLUSIONS
We conclude that SOX9 is required for the differentiation of Paneth cells. Our results elucidate an essential step in the differentiation of gut epithelium.
Department of Molecular Geneticsm, The University of Texas, M. D. Anderson Cancer Center, Houston, Texas, USA.
Yuko
Y
Mori-Akiyama
Maaike
M
van den Born
Johan H
JH
van Es
Stanley R
SR
Hamilton
Henry P
HP
Adams
Jiexin
J
Zhang
Hans
H
Clevers
Benoit
B
de Crombrugghe
D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000378:metabolism*; D006609:High Mobility Group Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008871:Microvilli / Q000378:metabolism; D019879:Paneth Cells / Q000378:metabolism*; D010641:Phenotype; D055758:SOX9 Transcription Factor; D013997:Time Factors; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D006609:High Mobility Group Proteins; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; D014157:Transcription Factors