An Autism Spectrum Disorder Susceptibility Gene, TAO2, is Important for Basal Dendrite Formation in the Neocortex

Abstract

How neurons develop their morphology is an important question in neurobiology. Here we describe a novel pathway that specifically affects the formation of basal dendrites and axonal projections in cortical pyramidal neurons. We report that thousand-and-one-amino acid 2 (TAO2) kinase plays an essential role in dendrite morphogenesis. TAO2 down-regulation impairs basal dendrite formation in vivo without affecting apical dendrites. Moreover, TAO2 interacts with Neuropilin 1 (Npn1), a receptor protein that binds the secreted guidance cue Semaphorin 3A (Sema3A). TAO2 over-expression restores dendrite formation in cultured cortical neurons from Npn1Sema− mice, which express Npn1 receptors incapable of binding Sema3A. TAO2 over-expression also ameliorates the basal dendrite impairment resulting from Npn1 down-regulation in vivo. Finally, Sema3A and TAO2 modulate the formation of basal dendrites through the activation of the c-Jun N-Terminal Kinase (JNK). These results delineate a pathway whereby Sema3A and Npn1 transduce signals through TAO2 and JNK to regulate basal dendrite development in cortical neurons.