Roles of Armadillo, a Drosophila catenin, during central nervous system development.

Neural development requires that neurons communicate and co-operate with one another and with other cell types in their environment. Drosophila Armadillo and its vertebrate homolog beta-catenin have dual roles in epithelial cells: transducing signals from the Wingless/Wnt family of proteins and working with cadherins to mediate cell adhesion. Wingless/Wnt signaling also directs certain cell fates in the central nervous system (CNS), and cadherins and catenins are thought to function together during neural development. We identified and analyzed the biochemical properties of a second armadillo isoform, with a truncated carboxyl terminus generated by alternative splicing. This isoform was found to accumulate in differentiating neurons. Using armadillo alleles that selectively inactivate the cell adhesion or the Wingless signaling functions of Armadillo, we found that Armadillo had two sequential roles in neural development. Armadillo function in Wingless signal transduction was required early in development for determination of neuroblast fate. Later in development, disruption of the cell-cell adhesion function of Armadillo resulted in subtle defects in the construction of the axonal scaffold. Mutations in the gene encoding the Drosophila tyrosine kinase Abelson substantially enhanced the severity of the CNS phenotype of armadillo mutations, consistent with these proteins functioning co-operatively at adherens junctions in both the CNS and the epidermis. This is one of the first demonstrations of a role for the cadherin-catenin system in the normal development of the CNS. The genetic interactions between armadillo and abelson point to a possible role for the tyrosine kinase Abelson in cell-cell adhesive junctions in both the CNS and the epidermis.