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Cadherins are critical for the radial migration of excitatory projection neurons into the developing neocortical wall. However, the specific cadherins and the signaling pathways that regulate radial migration are not well understood. Here we show that cadherin 2 (CDH2) and CDH4 cooperate to regulate radial migration via the protein tyrosine phosphatase 1B (PTP1B) and α- and β-catenins. Surprisingly, perturbation of cadherin-mediated signaling does not affect the formation and extension of leading processes of migrating neocortical neurons. Instead, movement of the cell body and nucleus (nucleokinesis) is disrupted. This defect is partially rescued by overexpression of LIS1, a microtubule associated protein that has previously been shown to regulate nucleokinesis. Taken together our findings indicate that cadherin-mediated signaling to the cytoskeleton is critical for nucleokinesis of neocortical projection neurons during their radial migration.

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Molecular and Cellular Neuroscience Department, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA 92037, USA Present address: Division of Neuroscience, School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK