Asymmetric centrosome inheritance maintains neural progenitors in the neocortex

Xiaoqun Wang, Jin-Wu Tsai, Janice H. Imai, Wei-Nan Lian, Richard B. Vallee and Song-Hai Shi
Additional contact information
Xiaoqun Wang: Developmental Biology Program, Memorial Sloan Kettering Cancer Centre, 1275 York Avenue, New York, New York 10065, USA
Jin-Wu Tsai: Columbia University, 630 W. 168th Street, New York, New York 10032, USA
Janice H. Imai: Developmental Biology Program, Memorial Sloan Kettering Cancer Centre, 1275 York Avenue, New York, New York 10065, USA
Wei-Nan Lian: Columbia University, 630 W. 168th Street, New York, New York 10032, USA
Richard B. Vallee: Columbia University, 630 W. 168th Street, New York, New York 10032, USA
Song-Hai Shi: Developmental Biology Program, Memorial Sloan Kettering Cancer Centre, 1275 York Avenue, New York, New York 10065, USA

Nature, 2009, vol. 461, issue 7266, 947-955

Abstract: Abstract Asymmetric divisions of radial glia progenitors produce self-renewing radial glia and differentiating cells simultaneously in the ventricular zone (VZ) of the developing neocortex. Whereas differentiating cells leave the VZ to constitute the future neocortex, renewing radial glia 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 in the embryonic mouse neocortex. Centrosome duplication in dividing radial glia 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 glia 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 indicate that preferential inheritance of the centrosome with the mature older mother centriole is required for maintaining radial glia progenitors in the developing mammalian neocortex.

Date: 2009
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DOI: 10.1038/nature08435

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