Cdx2 determines the fate of postnatal intestinal endoderm

Emma J. Stringer, Isabelle Duluc, Thoueiba Saandi, Irwin Davidson, Monika Bialecka, Toshiro Sato, Nick Barker, Hans Clevers, Catrin A. Pritchard, Doug J. Winton, Nicholas A. Wright, Jean Noel Freund, Jacqueline Deschamps, Felix Beck

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Knock out of intestinal Cdx2 produces different effects depending upon the developmental stage at which this occurs. Early in development it produces histologically ordered stomach mucosa in the midgut. Conditional inactivation of Cdx2 in adult intestinal epithelium, as well as specifically in the Lgr5-positive stem cells, of adult mice allows long-term survival of the animals but fails to produce this phenotype. Instead, the endodermal cells exhibit cell-autonomous expression of gastric genes in an intestinal setting that is not accompanied by mesodermal expression of Barx1, which is necessary for gastric morphogenesis. Cdx2- negative endodermal cells also fail to express Sox2, a marker of gastric morphogenesis. Maturation of the stem cell niche thus appears to be associated with loss of ability to express positional information cues that are required for normal stomach development. Cdx2-negative intestinal crypts produce subsurface cystic vesicles, whereas untargeted crypts hypertrophy to later replace the surface epithelium. These observations are supported by studies involving inactivation of Cdx2 in intestinal crypts cultured in vitro. This abolishes their ability to form long-term growing intestinal organoids that differentiate into intestinal phenotypes. We conclude that expression of Cdx2 is essential for differentiation of gut stem cells into any of the intestinal cell types, but they maintain a degree of cell-autonomous plasticity that allows them to switch on a variety of gastric genes.

Original languageEnglish
Pages (from-to)465-474
Number of pages10
JournalDevelopment
Volume139
Issue number3
DOIs
Publication statusPublished - 2012 Feb 1
Externally publishedYes

Keywords

  • Barx1
  • Cdx2
  • Endoderm
  • Intestine
  • Mesoderm
  • Mouse
  • Stem cell

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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  • Cite this

    Stringer, E. J., Duluc, I., Saandi, T., Davidson, I., Bialecka, M., Sato, T., Barker, N., Clevers, H., Pritchard, C. A., Winton, D. J., Wright, N. A., Freund, J. N., Deschamps, J., & Beck, F. (2012). Cdx2 determines the fate of postnatal intestinal endoderm. Development, 139(3), 465-474. https://doi.org/10.1242/dev.070722