An Unconventional Kinesin and Cytoplasmic Dynein Are Responsible for Interkinetic Nuclear Migration in Neural Stem Cells

Radial glial progenitor cells (RGPCs), have been long known to exhibit a striking form of bidirectional nuclear migration. The purpose and underlying mechanism for this unusual cell cycle-dependent “interkinetic” nuclear migration has remained poorly understood. We investigated the basis for this behavior by live imaging of nuclei, centrosomes, and microtubules in embryonic rat brain slices, coupled with blebbistatin and RNAi. We observed nuclei to migrate independent of centrosomes and unidirectionally away from or toward the ventricular surface along microtubules, which we found to be uniformly oriented from the ventricular to the pial surfaces of the brain. Cytoplasmic dynein RNAi specifically inhibited apically-directed nuclear movement. An RNAi screen for kinesin genes identified KIF1A, a member of the kinesin 3 family, as the motor for basally-directed nuclear movement. These observations provide the first direct evidence for a role for kinesins in nuclear migration and neurogenesis, and suggest that a novel cell cycle-dependent switch between distinct microtubule motors drives INM.