p27(Kip1) is a microtubule-associated protein that promotes microtubule polymerization during neuron migration.

The migration of cortical interneurons is characterized by extensive morphological changes that result from successive cycles of nucleokinesis and neurite branching. Their molecular bases remain elusive, and the present work describes how p27(Kip1) controls cell-cycle-unrelated signaling pathways to regulate these morphological remodelings. Live imaging reveals that interneurons lacking p27(Kip1) show delayed tangential migration resulting from defects in both nucleokinesis and dynamic branching of the leading process. At the molecular level, p27(Kip1) is a microtubule-associated protein that promotes polymerization of microtubules in extending neurites, thereby contributing to tangential migration. Furthermore, we show that p27(Kip1) controls actomyosin contractions that drive both forward translocation of the nucleus and growth cone splitting. Thus, p27(Kip1) cell-autonomously controls nucleokinesis and neurite branching by regulating both actin and microtubule cytoskeletons.