| First Author | Wang Y | Year | 2007 |
| Journal | Proc Natl Acad Sci U S A | Volume | 104 |
| Issue | 27 | Pages | 11328-33 |
| PubMed ID | 17592150 | Mgi Jnum | J:122831 |
| Mgi Id | MGI:3715578 | Doi | 10.1073/pnas.0702665104 |
| Citation | Wang Y, et al. (2007) Enteroendocrine precursors differentiate independently of Wnt and form serotonin expressing adenomas in response to active beta-catenin. Proc Natl Acad Sci U S A 104(27):11328-33 |
| abstractText | Wnt signaling is required for the maintenance of intestinal stem cells and self-renewal of the intestinal epithelium. Intestinal cancers are frequently associated with mutations that activate the Wnt pathway. The role of Wnt signaling on differentiation of lineage-specific precursors in the intestine is not well characterized. Here, we show that specification of enteroendocrine but not Paneth cells occurs independently of Wnt signals by conditional deletion of beta-catenin in immature cells expressing the transcription factor, neurogenin 3. In addition, we determined whether neurogenin 3-expressing cells respond to abnormal Wnt signaling. Activation of the Wnt pathway by conditionally deleting exon 3 of the beta-catenin gene at an early stage of enteroendocrine cell differentiation induced small-intestinal adenomas expressing serotonin, a feature not previously described in other tumors induced by Wnt in mice. In contrast, excision of exon 3 of beta-catenin at a later stage of enteroendocrine differentiation did not produce tumors. These results provide direct evidence that some intestinal lineages are specified independently of the Wnt pathway and may lead to a better understanding of the spectrum of neuroendocrine differentiation frequently seen in human gastrointestinal cancer. |
