Cadherin inhibition of beta-catenin signaling regulates the proliferation and differentiation of neural precursor cells.

The generation and differentiation of neurons during development requires coordination of intercellular interactions with spatio-temporal changes in gene expression. To examine the role of adhesion in cerebral cortical development, we overexpressed full-length cadherin and dominant-negative truncated cadherin in mouse cortical precursors. Full-length cadherin allowed for the maintenance of cell contact between daughter cells following cell division while dominant-negative cadherin decreased cell contact. Paradoxically, both cadherin isoforms inhibited precursor proliferation, induced premature neuronal differentiation, and inhibited beta-catenin dependent signaling. Furthermore, alteration of cadherin or beta-catenin function led to additional changes in precursor identity and division symmetry as demonstrated by altered expression of the radial glial marker, Pax6, and the intermediate precursor marker, Tbr2. Moreover, clonal analysis demonstrated asymmetric distribution of Tbr2 following precursor mitosis. Together, these results show that cadherins affect neural precursor fate determination through a cell-autonomous regulation of catenin signaling distinct from cadherin adhesive function.