| First Author | Ulloa F | Year | 2007 |
| Journal | Curr Biol | Volume | 17 |
| Issue | 6 | Pages | 545-50 |
| PubMed ID | 17331723 | Mgi Jnum | J:121269 |
| Mgi Id | MGI:3709704 | Doi | 10.1016/j.cub.2007.01.062 |
| Citation | Ulloa F, et al. (2007) Inhibitory Gli3 activity negatively regulates Wnt/beta-catenin signaling. Curr Biol 17(6):545-50 |
| abstractText | The Hedgehog (Hh) and Wingless (Wnt) families of secreted signaling molecules have key roles in embryonic development and adult tissue homeostasis [1-3]. In the developing neural tube, Wnt and Shh, emanating from dorsal and ventral regions, respectively, have been proposed to govern the proliferation and survival of neural progenitors [4-10]. Surprisingly, Shh is required for the growth and survival of cells in both ventral and dorsal neural tube [11]. Here we demonstrate that inhibition of Shh signaling causes a reduction in Wnt-mediated transcriptional activation. This reduction requires Gli3. Assays in embryos and cell lines indicate that repressor forms of the Hh-regulated transcription factor, Gli3 (Gli3R), which are generated in the absence of Hh signaling, inhibit canonical Wnt signaling. Gli3R acts by antagonizing active forms of the Wnt transcriptional effector, beta-catenin. Consistent with this, Gli3R appears to physically interact with the carboxy-terminal domain of beta-catenin, a region that includes the transactivation domain. These data offer an explanation for the proliferative defects in Shh null embryos and suggest a novel mechanism for crosstalk between the Hh and Wnt pathways. |
