Autism spectrum disorder susceptibility gene TAOK2 affects basal dendrite formation in the neocortex

1 0 2 2 VOLUME 15 | NUMBER 7 | JULY 2012 nature neurOSCIenCe a r t I C l e S Pyramidal neurons are abundant in brain regions associated with complex cognitive functions, including the cortex, hippocampus and amygdala 1 . An understanding of the distinct physiology and morphology of these neurons is key to the elucidation of the mechanisms underlying sophisticated cognitive functions in normal and disease conditions. Several lines of evidence suggest that aberrant dendritic arborization may contribute to neurodevelopmental and psychiatric disorders with delayed onset, such as autism spectrum disorders 2,3 . In general, pyramidal neurons have a dendritic tree that is divided into two domains: the apical dendrite, which extends toward the pial surface, and basal dendrites, which emerge from the base of the cell body. The majority of synapses received by neocortical pyramidal neurons form on the basal dendrites 4 . However, little is known about the molecular pathways that control the formation of basal dendrites. TAOK1 and TAOK2 serine/threonine protein kinases are known to activate mitogen-activated protein (MAP) kinase (MAPK) pathways (JNK, p38 or extracellular signal-regulated kinase Here we demonstrate that TAOK2 downregulation selectively impairs the formation of basal dendrites and axonal elongation. We found that TAOK2 interacted with Nrp1, the receptor of the secreted guidance cue Sema3A that controls basal dendrite arborization RESULTS Expression profile of TAOK2 in neurons and cerebral cortex To examine the subcellular expression profile of TAOK2, we analyzed TAOK2 immunoreactivity in mouse cortical neurons dissociated at embryonic day (E) 17 and cultured 2 days in vitro (DIV). TAOK2 preferentially localized to growth cone