Differential Regulation of Microtubule Severing by APC Underlies Distinct Patterns of Projection Neuron and Interneuron Migration

• Migration of interneurons (INs), but not projection neurons (PNs), depends on APC
• APC differentially modulates microtubule (MT) severing in INs and PNs
• APC affects the stability of the MT-severing enzyme p60-katanin in INs, but not in PNs
• Regulation of MT severing facilitates distinct modes of cortical neuronal migration

SummaryCoordinated migration of distinct classes of neurons to appropriate positions leads to the formation of functional neuronal circuitry in the cerebral cortex. The two major classes of cortical neurons, interneurons and projection neurons, utilize distinctly different modes (radial versus tangential) and routes of migration to arrive at their final positions in the cerebral cortex. Here, we show that adenomatous polyposis coli (APC) modulates microtubule (MT) severing in interneurons to facilitate tangential mode of interneuron migration, but not the glial-guided, radial migration of projection neurons. APC regulates the stability and activity of the MT-severing protein p60-katanin in interneurons to promote the rapid remodeling of neuronal processes necessary for interneuron migration. These findings reveal how severing and restructuring of MTs facilitate distinct modes of neuronal migration necessary for laminar organization of neurons in the developing cerebral cortex.