Neurogenin2 regulates the initial axon guidance of cortical pyramidal neurons projecting medially to the corpus callosum

BACKGROUND: The formation of the mammalian central nervous system requires the establishment of complex neural circuits between a diverse array of neuronal subtypes. Here we report that the proneural transcription factor Neurogenin2 (Ngn2) is crucial for the proper specification of cortical axon projections. RESULTS: The genetic loss of Ngn2 in mice results in fewer callosal axons projecting towards the midline as well as abnormal midline crossing. shRNA-mediated knockdown of Ngn2 revealed its cell-autonomous requirement for the proper projection of axons from layer 2/3 pyramidal neurons to the midline in vivo. We found that the acute loss of Ngn2 in vivo induces the axon of superficial layer 2/3 neurons to project laterally towards aberrant cortical and subcortical targets. CONCLUSIONS: These and previous results demonstrate that Ngn2 is required for the coordinated specification of cardinal features defining the phenotype of cortical pyramidal neurons, including their migration properties, dendritic morphology and axonal projection.