Bmp signaling is required for intestinal growth and morphogenesis

Lorene E. Batts, D. Brent Polk, Raymond N. Dubois, Holger Kulessa, Brigid Hogan

Research output: Contribution to journalArticlepeer-review

110 Scopus citations

Abstract

Intestinal growth, morphogenesis, differentiation, and homeostasis are regulated by reciprocal interactions between the epithelium and the underlying mesenchymal stroma. The identification of BMPR1A mutations in patients with Juvenile Polyposis implicates Bmp signaling as an important mediator of these interactions. To test this hypothesis, we inhibited Bmp signalling in the mouse proximal intestine by transgenic misexpression of the BMP antagonist, noggin, using regulatory elements of the fatty acid binding protein (Fabp1) gene. This leads to abnormal villus morphogenesis, stromal and epithelial hyperplasia, and ectopic crypt formation. The resulting intestinal histopathology resembles that seen in human Juvenile Polyposis. Misexpression of noggin in the large intestine gives a similar abnormal phenotype in this region of the gut. Analysis of gene expression in the transgenic small intestine raises the possibility that Hedgehog and Pdgf signaling play a role in the development of the Juvenile Polyposis-like phenotype.

Original languageEnglish (US)
Pages (from-to)1563-1570
Number of pages8
JournalDevelopmental Dynamics
Volume235
Issue number6
DOIs
StatePublished - Jun 2006
Externally publishedYes

Keywords

  • Bone morphogenetic proteins
  • Growth control
  • Intestine
  • Juvenile polyposis
  • Morphogenesis
  • Transgenic mouse

ASJC Scopus subject areas

  • Developmental Biology

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