Kinesin 3 and cytoplasmic dynein mediate interkinetic nuclear migration in neural stem cells

• DOI: 10.1038/nn.2665
• Publication Date: 2010-11-01T10:03:09Z
• Authors: Jin-Wu Tsai; Wei-Nan Lian; Shahrnaz Kemal; Arnold R Kriegstein; Richard B Vallee
• Keywords: Cytoplasmic Dyneins; 0301 basic medicine; 1.1 Normal biological development and functioning; Biological Psychology; Kinesins; Microtubules; PC12 Cells; 03 medical and health sciences; Neural Stem Cells; Underpinning research; Cell Movement; Psychology; Animals; Embryonic Stem Cells; Pediatric; Cell Nucleus; Neurology & Neurosurgery; Biomedical and Clinical Sciences; Cell Cycle; Neurosciences; Kinesin; Brain Disorders; Kinesis; Rats; Neurological; Congenital Structural Anomalies; Biological psychology; Cognitive Sciences

Radial glial progenitor cells exhibit bidirectional cell cycle-dependent nuclear oscillations. The purpose and underlying mechanism of this unusual 'interkinetic nuclear migration' are poorly understood. We investigated the basis for this behavior by live imaging of nuclei, centrosomes and microtubules in embryonic rat brain slices, coupled with the use of RNA interference (RNAi) and the myosin inhibitor blebbistatin. We found that nuclei migrated independent of centrosomes and unidirectionally away from or toward the ventricular surface along microtubules, which were uniformly oriented from the ventricular surface to the pial surface of the brain. RNAi directed against cytoplasmic dynein specifically inhibited nuclear movement toward the apical surface. An RNAi screen of kinesin genes identified Kif1a, a member of the kinesin-3 family, as the motor for basally directed nuclear movement. These observations provide direct evidence that kinesins are involved in nuclear migration and neurogenesis and suggest that a cell cycle-dependent switch between distinct microtubule motors drives interkinetic nuclear migration.