β-catenin function is required for cerebellar morphogenesis

Because of the failure to form embryonic mid–hindbrain structures in conventional Wnt1 knockout animals, ongoing roles for Wnt signaling at later stages have been difficult to resolve. Here, we used Nestin-cre to ablate β-catenin at midgestation in developing CNS precursors to investigate β-catenin-dependent Wnt signaling in the development of late-derived structures such as the cerebellum. At 14.5 dpc, we found evidence for premature neural precursor cell fate commitment. At P0, we observed vermian hypoplasia and failure to fuse the cerebellar hemispheres and caudal midbrain, a phenotype reminiscent of the swaying (Wnt1sw/sw) mouse mutant. Our findings indicate general functions for β-catenin beyond the neural plate stage during brain development and a particular role for β-catenin-dependent Wnt signaling during morphogenesis of the caudal midbrain and the cerebellum. We discuss our results with respect to genetic pathways that regulate formation of derivatives of the embryonic midbrain–hindbrain region.