How neurons develop their morphology is an important question in neurobiology. Here we describe a new 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 kinase (TAOK2), also known as TAO2, is essential for dendrite morphogenesis. TAOK2 downregulation impairs basal dendrite formation in vivo without affecting apical dendrites. Moreover, TAOK2 interacts with Neuropilin 1 (Nrp1), a receptor protein that binds the secreted guidance cue Semaphorin 3A (Sema3A). TAOK2 overexpression restores dendrite formation in cultured cortical neurons from Nrp1Sema− mice, which express Nrp1 receptors incapable of binding Sema3A. TAOK2 overexpression also ameliorates the basal dendrite impairment resulting from Nrp1 downregulation in vivo. Finally, Sema3A and TAOK2 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 Nrp1 transduce signals through TAOK2 and JNK to regulate basal dendrite development in cortical neurons.
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We thank A. Mungenast, E.J. Kwon, M.H. Cobb (University of Texas Southwestern Medical Center) and Y. Gotoh (University of Tokyo) for critical reading of the manuscript, providing vectors, antibodies, and suggestions. The Simons Foundation Autism Research Initiative supported this work. F.C.d.A. is supported by a postdoctoral fellowship from the Simons Foundation (Simons Center for the Social Brain, Massachusetts Institute of Technology). US National Institutes of Health grant R01 MH59199 to A.L.K. and D.D.G. supported this work. L.-H.T., A.L.K. and D.D.G. are investigators of the Howard Hughes Medical Institute.
The authors declare no competing financial interests.
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Calderon de Anda, F., Rosario, A., Durak, O. et al. Autism spectrum disorder susceptibility gene TAOK2 affects basal dendrite formation in the neocortex. Nat Neurosci 15, 1022–1031 (2012). https://doi.org/10.1038/nn.3141
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