Neuronal migration is crucial for mammalian brain development. In many migrating neurons, the nucleus translocates from the trailing to the leading edge of the cell in a manner dependent on the actin and microtubule cytoskeletons; however, how these cytoskeletons interact during nuclear translocation, and their relative contribution to the forces that drive it, has remained unclear. Now, Hiroki Umeshima, Mineko Kengaku and colleagues use high-resolution time-lapse imaging of cerebellar granule cell (CGC) cultures to study the cytoskeletal mechanics of nuclear translocation during migration. Surprisingly, as CGCs migrate their nuclei actively rotate, in a manner not linked to the motion of centrosomes. Depolymerisation of microtubule filaments reduces rotation and translocation, but, by contrast, blocking actomyosin contractility affects translocation but not rotation. The microtubule motors dynein and kinesin-1 are the driving forces for nuclear rotation and act on the nucleus through the LINC complex. Arrays of mixed polarity microtubules are observed moving across the nucleus, and the authors show that disruption of kinesin-1 leads to a failure of normal CGC migration in vivo. Together, this study describes a novel cell behaviour during neuronal migration, and expands our understanding of the relative contribution of the actin and microtubule cytoskeletons during brain development.
