Abstract
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.
Original language | English |
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Pages (from-to) | 545-550 |
Number of pages | 6 |
Journal | Current Biology |
Volume | 17 |
Issue number | 6 |
Early online date | 1 Mar 2007 |
DOIs | |
Publication status | Published - 20 Mar 2007 |
Keywords
- Animals
- Chick Embryo
- Embryo, Mammalian
- Embryo, Nonmammalian
- Embryonic Development
- Gene Expression Regulation
- Hedgehog Proteins
- Humans
- Kruppel-Like Transcription Factors
- Mice
- Nerve Tissue Proteins
- Protein Interaction Mapping
- Signal Transduction
- Wnt Proteins
- Wnt3 Protein
- Xenopus
- beta Catenin