N- and C-Terminal Domains of β-Catenin, Respectively, Are Required to Initiate and Shape Axon Arbors of Retinal Ganglion CellsIn Vivo

Abstract

We used deletion mutants to study beta-catenin function in axon arborization of retinal ganglion cells (RGCs) in live Xenopus laevis tadpoles. A deletion mutant betacatDeltaARM consists of the N- and C-terminal domains of wild-type beta-catenin that contain, respectively, alpha-catenin and postsynaptic density-95 (PSD-95)/discs large (Dlg)/zona occludens-1 (ZO-1) (PDZ) binding sites but lacks the central armadillo repeat region that binds cadherins and other proteins. Expression of DeltaARM in RGCs of live tadpoles perturbed axon arborization in two distinct ways: some RGC axons did not form arbors, whereas the remaining RGC axons formed arbors with abnormally long and tangled branches. Expression of the N- and C-terminal domains of beta-catenin separately in RGCs resulted in segregation of these two phenotypes. The axons of RGCs overexpressing the N-terminal domain of beta-catenin developed no or very few branches, whereas axons of RGCs overexpressing the C-terminal domain of beta-catenin formed arbors with long, tangled branches. Additional analysis revealed that the axons of RGCs that did not form arbors after overexpression of DeltaARM or the N-terminal domain of beta-catenin were frequently mistargeted within the tectum. These results suggest that interactions of the N-terminal domain of beta-catenin with alpha-catenin and of the C-terminal domain with PDZ domain-containing proteins are required, respectively, to initiate and shape axon arbors of RGCs in vivo.