Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2000-7-24
pubmed:abstractText
The gastrointestinal tract develops from the embryonic gut, which is composed of an endodermally derived epithelium surrounded by cells of mesodermal origin. Cell signaling between these two tissue layers appears to play a critical role in coordinating patterning and organogenesis of the gut and its derivatives. We have assessed the function of Sonic hedgehog and Indian hedgehog genes, which encode members of the Hedgehog family of cell signals. Both are expressed in gut endoderm, whereas target genes are expressed in discrete layers in the mesenchyme. It was unclear whether functional redundancy between the two genes would preclude a genetic analysis of the roles of Hedgehog signaling in the mouse gut. We show here that the mouse gut has both common and separate requirements for Sonic hedgehog and Indian hedgehog. Both Sonic hedgehog and Indian hedgehog mutant mice show reduced smooth muscle, gut malrotation and annular pancreas. Sonic hedgehog mutants display intestinal transformation of the stomach, duodenal stenosis (obstruction), abnormal innervation of the gut and imperforate anus. Indian hedgehog mutants show reduced epithelial stem cell proliferation and differentiation, together with features typical of Hirschsprung's disease (aganglionic colon). These results show that Hedgehog signals are essential for organogenesis of the mammalian gastrointestinal tract and suggest that mutations in members of this signaling pathway may be involved in human gastrointestinal malformations.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0950-1991
pubmed:author
pubmed:issnType
Print
pubmed:volume
127
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2763-72
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10821773-Animals, pubmed-meshheading:10821773-Body Patterning, pubmed-meshheading:10821773-Cell Differentiation, pubmed-meshheading:10821773-Cell Division, pubmed-meshheading:10821773-Crosses, Genetic, pubmed-meshheading:10821773-Digestive System, pubmed-meshheading:10821773-Digestive System Abnormalities, pubmed-meshheading:10821773-Embryonic Induction, pubmed-meshheading:10821773-Gene Expression Regulation, Developmental, pubmed-meshheading:10821773-Hedgehog Proteins, pubmed-meshheading:10821773-Humans, pubmed-meshheading:10821773-Mice, pubmed-meshheading:10821773-Mice, Inbred CBA, pubmed-meshheading:10821773-Mice, Inbred Strains, pubmed-meshheading:10821773-Mice, Knockout, pubmed-meshheading:10821773-Morphogenesis, pubmed-meshheading:10821773-Proteins, pubmed-meshheading:10821773-Trans-Activators
pubmed:year
2000
pubmed:articleTitle
Hedgehog signals regulate multiple aspects of gastrointestinal development.
pubmed:affiliation
Department of Molecular and Cellular Biology, and Howard Hughes Medical Institute, Harvard University, Divinity Avenue, Cambridge, Massachusetts 02138, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't