| First Author | Olson LE | Year | 2006 |
| Journal | Cell | Volume | 125 |
| Issue | 3 | Pages | 593-605 |
| PubMed ID | 16678101 | Mgi Jnum | J:114817 |
| Mgi Id | MGI:3690195 | Doi | 10.1016/j.cell.2006.02.046 |
| Citation | Olson LE, et al. (2006) Homeodomain-mediated beta-catenin-dependent switching events dictate cell-lineage determination. Cell 125(3):593-605 |
| abstractText | While the biological roles of canonical Wnt/beta-catenin signaling in development and disease are well documented, understanding the molecular logic underlying the functionally distinct nuclear transcriptional programs mediating the diverse functions of beta-catenin remains a major challenge. Here, we report an unexpected strategy for beta-catenin-dependent regulation of cell-lineage determination based on interactions between beta-catenin and a specific homeodomain factor, Prop1, rather than Lef/Tcfs. beta-catenin acts as a binary switch to simultaneously activate expression of the critical lineage-determining transcription factor, Pit1, and to repress the gene encoding the lineage-inhibiting transcription factor, Hesx1, acting via TLE/Reptin/HDAC1 corepressor complexes. The strategy of functionally distinct actions of a homeodomain factor in response to Wnt signaling is suggested to be prototypic of a widely used mechanism for generating diverse cell types from pluripotent precursor cells in response to common signaling pathways during organogenesis. |
