Bmp signaling is required for intestinal growth and morphogenesis.
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 signaling 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.
Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Lorene E
LE
Batts
D Brent
DB
Polk
Raymond N
RN
Dubois
Holger
H
Kulessa
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics*; D050556:Fatty Acid-Binding Proteins / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D007422:Intestines / Q000002:abnormalities / Q000196:embryology*; D051379:Mice; D008822:Mice, Transgenic; D000099176:Noggin Protein
D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D050556:Fatty Acid-Binding Proteins; D000099176:Noggin Protein; C493320:Fabp1 protein, mouse