Asymmetric centrosome inheritance maintains neural progenitors in the neocortex

Abstract

Asymmetric divisions of radial glial progenitors produce self-renewing radial glia and differentiating cells simultaneously in the ventricular zone (VZ) of the developing neocortex. While differentiating cells leave the VZ to constitute the future neocortex, renewing radial glial progenitors stay in the VZ for subsequent divisions. The differential behaviour of progenitors and their differentiating progeny is essential for neocortical development; however, the mechanisms that ensure these behavioural differences are unclear. Here we show that asymmetric centrosome inheritance regulates the differential behaviour of renewing progenitors and their differentiating progeny. Centrosome duplication in dividing radial glial progenitors generates a pair of centrosomes with differently aged mother centrioles. During peak phases of neurogenesis, the centrosome retaining the old mother centriole stays in the VZ and is preferentially inherited by radial glial progenitors, whereas the centrosome containing the new mother centriole mostly leaves the VZ and is largely associated with differentiating cells. Removal of Ninein, a mature centriole-specific protein, disrupts the asymmetric segregation and inheritance of the centrosome and causes premature depletion of progenitors from the VZ. These results suggest that preferential inheritance of the centrosome with the mature older mother centriole is required for maintaining radial glial progenitors in the developing mammalian neocortex.