SOX9 Is Required for the Differentiation of Paneth Cells in the Intestinal Epithelium

Background & Aims: 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.

Abbreviations used in this paper: BrdU, bromodeoxyuridine, PCR, polymerase chain reaction, PBS, phosphate buffered saline, SSC, standard saline citrate, PAS, periodic acid-Schiff, TUNEL, terminal deoxynucleotidyl transferase-mediated deoxyurdine triphosphate nick-end labeling