N- and C-terminal domains of beta-catenin, respectively, are required to initiate and shape axon arbors of retinal ganglion cells in vivo.
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.
Elul
Tamira M
TM
Department of Physiology, University of California San Francisco, San Francisco, California 94143, USA. tamira@itsa.ucsf.edu
Kimes
Nikole E
NE
Kohwi
Minoree
M
Reichardt
Louis F
LF
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D015820:Cadherins / Q000096:biosynthesis; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D049452:Green Fluorescent Proteins; D007814:Larva; D008164:Luminescent Proteins; D016297:Mutagenesis, Site-Directed; D019581:Neuropil / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000502:physiology; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism*; D013477:Superior Colliculi / Q000166:cytology / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D029867:Xenopus Proteins; D014982:Xenopus laevis; D051176:beta Catenin
C495266:CTNNB1 protein, Xenopus; D015820:Cadherins; D003598:Cytoskeletal Proteins; D008164:Luminescent Proteins; D015534:Trans-Activators; D029867:Xenopus Proteins; D051176:beta Catenin; D049452:Green Fluorescent Proteins