title: Asymmetric centrosome inheritance maintains neural progenitors in the neocortex.
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.
authors.affiliation: Developmental Biology Program, Memorial Sloan Kettering Cancer Centre, 1275 York Avenue, New York, New York 10065, USA.
authors.forename: Xiaoqun
authors.initials: X
authors.lastname: Wang
authors.forename: Jin-Wu
authors.initials: JW
authors.lastname: Tsai
authors.forename: Janice H
authors.initials: JH
authors.lastname: Imai
authors.forename: Wei-Nan
authors.initials: WN
authors.lastname: Lian
authors.forename: Richard B
authors.initials: RB
authors.lastname: Vallee
authors.forename: Song-Hai
authors.initials: SH
authors.lastname: Shi
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D019070:Cell Lineage; D016922:Cellular Senescence / Q000502:physiology; D002502:Centrioles / Q000502:physiology; D018385:Centrosome / Q000502:physiology*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D006801:Humans; D051379:Mice; D019579:Neocortex / Q000166:cytology* / Q000196:embryology; D055495:Neurogenesis / Q000502:physiology; D009457:Neuroglia / Q000166:cytology; D009474:Neurons / Q000166:cytology*; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D013234:Stem Cells / Q000166:cytology*
chemical_list: D002135:Calcium-Binding Proteins; D002868:Chromosomal Proteins, Non-Histone; D003598:Cytoskeletal Proteins; C099035:Nin protein, mouse; D009687:Nuclear Proteins; C056608:caltractin