Inactivation of the beta-catenin gene by Wnt1-Cre-mediated deletion results in dramatic brain malformation and failure of craniofacial development.
beta-Catenin is a central component of both the cadherin-catenin cell adhesion complex and the Wnt signaling pathway. We have investigated the role of beta-catenin during brain morphogenesis, by specifically inactivating the beta-catenin gene in the region of Wnt1 expression. To achieve this, mice with a conditional ('floxed') allele of beta-catenin with required exons flanked by loxP recombination sequences were intercrossed with transgenic mice that expressed Cre recombinase under control of Wnt1 regulatory sequences. beta-Catenin gene deletion resulted in dramatic brain malformation and failure of craniofacial development. Absence of part of the midbrain and all of the cerebellum is reminiscent of the conventional Wnt1 knockout (Wnt1(-/-)), suggesting that Wnt1 acts through beta-catenin in controlling midbrain-hindbrain development. The craniofacial phenotype, not observed in embryos that lack Wnt1, indicates a role for beta-catenin in the fate of neural crest cells. Analysis of neural tube explants shows that (beta-catenin is efficiently deleted in migrating neural crest cell precursors. This, together with an increased apoptosis in cells migrating to the cranial ganglia and in areas of prechondrogenic condensations, suggests that removal of beta-catenin affects neural crest cell survival and/or differentiation. Our results demonstrate the pivotal role of beta-catenin in morphogenetic processes during brain and craniofacial development.
Pubmed ID: 11262227 RIS Download
Animals | Apoptosis | Biological Markers | Brain | Branchial Region | Cells, Cultured | Craniofacial Abnormalities | Cytoskeletal Proteins | Female | Ganglia, Spinal | Integrases | Male | Mesencephalon | Mice | Mice, Inbred C57BL | Mice, Knockout | Mutagenesis | Neural Crest | Proto-Oncogene Proteins | Rhombencephalon | Signal Transduction | Skull | Trans-Activators | Viral Proteins | Wnt Proteins | Wnt1 Protein | Zebrafish Proteins | beta Catenin