N- and C-terminal domains of β-catenin, respectively, are required to initiate and shape axon arbors of retinal ganglion cells in vivo

Abstract

We used deletion mutants to study β-catenin function in axon arborization of retinal ganglion cells (RGCs) in live Xenopus laevis tadpoles. A deletion mutant βcatΔARM consists of the N- and C-terminal domains of wild-type β-catenin that contain, respectively, α-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 ΔARM 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 β-catenin separately in RGCs resulted in segregation of these two phenotypes. The axons of RGCs overexpressing the N-terminal domain of β-catenin developed no or very few branches, whereas axons of RGCs overexpressing the C-terminal domain of β-catenin formed arbors with long, tangled branches. Additional analysis revealed that the axons of RGCs that did not form arbors after overexpression of ΔARM or the N-terminal domain of β-catenin were frequently mistargeted within the tectum. These results suggest that interactions of the N-terminal domain of β-catenin with α-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.