Abstract：
:Wnt signaling pathways have been demonstrated to play important roles in controlling tissue patterning and cell proliferation. In the gastrointestinal tract, mutations that lead to activation of the canonical Wnt pathway through beta-catenin result in familial and sporadic colon cancers. The downstream transcription factor Tcf4 is required to maintain the proliferative stem cell compartment in the crypts of the small intestine. Activation of TCF-dependent transcription is a good correlate to neoplastic transformation. Despite its association with cancer in the colon, little is known of the role for Wnt signaling during development and patterning of the gut tube. We conducted a comprehensive expression screen for Wnt signaling components during different stages of gut development in the chick. Conserved expression patterns of these genes indicate that they likely play essential roles in gut morphogenesis. Based on the expression profiles of putative components of each pathway, we are able to postulate specific roles for the various pathways during gut development. Predictions of roles for canonical signaling in the developing gizzard, duodenum, and large intestine in chick were tested by viral misexpression of dominant-negative (DN) forms of the downstream cofactors Tcf4 and Lef1. In the chick, Tcf4 is expressed in the posterior gizzard mesoderm. Misexpression of DN-Tcf4 in the splanchnic mesoderm resulted in the failure of the gizzard epithelium to form microvilli. Lef1 is expressed in the chick duodenum and large intestine mesoderm. Viral misexpression of DN-Lef1 resulted in diminished mesoderm and overproliferation of the large intestine endoderm, leading to stenosis of the lumen. The results from these misexpression studies in the chick, together with evidence from colorectal lesions, indicate that the canonical Wnt pathway plays critical roles in balancing cell proliferation versus cell differentiation during gut development. The expression profiles of the Wnt signaling components presented in this paper should prove valuable in deciphering additional roles of the Wnt pathways during patterning of the vertebrate gut tube.
journal_name
Dev Bioljournal_title
Developmental biologyauthors
Theodosiou NA,Tabin CJdoi
10.1016/s0012-1606(03)00185-4subject
Has Abstractpub_date
2003-07-15 00:00:00pages
258-71issue
2eissn
0012-1606issn
1095-564Xpii
S0012160603001854journal_volume
259pub_type
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journal_title：Developmental biology
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journal_title：Developmental biology
pub_type： 杂志文章
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pub_type： 杂志文章
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