SOX9 is required for the differentiation of paneth cells in the intestinal epithelium

Gastroenterology. 2007 Aug;133(2):539-46. doi: 10.1053/j.gastro.2007.05.020. Epub 2007 May 21.

Abstract

Background and 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation*
  • Cell Proliferation
  • Epithelial Cells / metabolism*
  • High Mobility Group Proteins / deficiency
  • High Mobility Group Proteins / genetics
  • High Mobility Group Proteins / metabolism*
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / growth & development
  • Intestinal Mucosa / metabolism*
  • Mice
  • Mice, Knockout
  • Microvilli / metabolism
  • Paneth Cells / metabolism*
  • Phenotype
  • SOX9 Transcription Factor
  • Time Factors
  • Transcription Factors / deficiency
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • High Mobility Group Proteins
  • SOX9 Transcription Factor
  • Sox9 protein, mouse
  • Transcription Factors