( B) GFP and F-actin immunostaining of cortical coronal sections from E12.5, E15.5, and P0 Pcdhα GFP mouse brain. Var, variable region Con, constant region EC, ectodomain VCD, variable cytoplasmic domain αCD, Pcdhα constant domain. ( A) Schematics of the mouse Pcdhα organization. VCD WAVE complex cell-adhesion kinase Pyk2 cortical neuron migration cytoskeletal dynamics mouse neuroscience protocadherin. Thus, we define a molecular Pcdhα/WAVE/Pyk2/Rac1 axis from protocadherin cell-surface receptors to actin cytoskeletal dynamics in cortical neuron migration and dendrite morphogenesis in mouse brain. In addition, overexpression of proline-rich tyrosine kinase 2 (Pyk2, also known as Ptk2b, Cakβ, Raftk, Fak2, and Cadtk), a non-receptor cell-adhesion kinase and scaffold protein downstream of Pcdhα, impairs cortical neuron migration via inactivation of the small GTPase Rac1. Here, we report that the protocadherin alpha ( Pcdha) gene cluster regulates neuronal migration during cortical development and cytoskeletal dynamics in primary cortical culture through the WAVE (Wiskott-Aldrich syndrome family verprolin homologous protein, also known as Wasf) complex. Diverse clustered protocadherins are thought to function in neurite morphogenesis and neuronal connectivity in the brain.
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