A novel mechanism for the transcriptional regulation of Wnt signaling in development
- 19 August 2011
- journal article
- Published by Cold Spring Harbor Laboratory
- Vol. 25 (17), 1783-1795
- https://doi.org/10.1101/gad.17227011
Abstract
Axial patterning of the embryonic brain requires a precise balance between canonical Wnt signaling, which dorsalizes the nervous system, and Sonic hedgehog (Shh), which ventralizes it. The ventral anterior homeobox (Vax) transcription factors are induced by Shh and ventralize the forebrain through a mechanism that is poorly understood. We therefore sought to delineate direct Vax target genes. Among these, we identify an extraordinarily conserved intronic region within the gene encoding Tcf7l2, a key mediator of canonical Wnt signaling. This region functions as a Vax2-activated internal promoter that drives the expression of dnTcf7l2, a truncated Tcf7l2 isoform that cannot bind β-catenin and that therefore acts as a potent dominant-negative Wnt antagonist. Vax2 concomitantly activates the expression of additional Wnt antagonists that cooperate with dnTcf7l2. Specific elimination of dnTcf7l2 in Xenopus results in headless embryos, a phenotype consistent with a fundamental role for this regulator in forebrain development.Keywords
This publication has 48 references indexed in Scilit:
- Sonic hedgehog functions through dynamic changes in temporal competence in the developing forebrainCurrent Opinion in Genetics & Development, 2010
- The balance of TCF7L2 variants with differential activities in Wnt-signaling is regulated by lithium in a GSK3β-independent mannerBiochemical and Biophysical Research Communications, 2010
- Wnt Signaling and the Polarity of the Primary Body AxisCell, 2009
- Wnt/β-Catenin Signaling: Components, Mechanisms, and DiseasesDevelopmental Cell, 2009
- Ocular coloboma and dorsoventral neuroretinal patterning defects in Lrp6 mutant eyesDevelopmental Dynamics, 2008
- An integrated software system for analyzing ChIP-chip and ChIP-seq dataNature Biotechnology, 2008
- TCF4 deficiency expands ventral diencephalon signaling and increases induction of pituitary progenitorsDevelopmental Biology, 2007
- Chromatin immunoprecipitation and microarray-based analysis of protein locationNature Protocols, 2006
- Dickkopf1 Is Required for Embryonic Head Induction and Limb Morphogenesis in the MouseDevelopmental Cell, 2001
- Neuronal specification in the spinal cord: inductive signals and transcriptional codesNature Reviews Genetics, 2000