title: Cortical neurogenesis in the absence of centrioles.
abstract: Neuronal production in the mammalian cortex depends on extensive mitoses of radial glial progenitors (RGPs) residing in the ventricular zone (VZ). We examined the function of centrioles in RGPs during cortical neurogenesis in mice by conditional removal of SAS-4, a protein that is required for centriole biogenesis. SAS-4 deletion led to a progressive loss of centrioles, accompanied by RGP detachment from the VZ. Delocalized RGPs did not become outer subventricular zone RGPs (oRGs). Although they remained proliferative, ectopic RGPs, as well as those in the VZ, with a centrosomal deficit exhibited prolonged mitosis, p53 upregulation and apoptosis, resulting in neuronal loss and microcephaly. Simultaneous removal of p53 fully rescued RGP death and microcephaly, but not RGP delocalization and randomized mitotic spindle orientation. Our findings define the functions of centrioles in anchoring RGPs in the VZ and ensuring their efficient mitoses, and reveal the robust adaptability of RGPs in the developing cortex.
authors.affiliation: 1] Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA. [2] Graduate Program in Neuroscience, Weill Cornell Medical College, New York, New York, USA. [3].
authors.forename: Ryan
authors.initials: R
authors.lastname: Insolera
authors.affiliation: 1] Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA. [2].
authors.forename: Hisham
authors.initials: H
authors.lastname: Bazzi
authors.affiliation: 1] Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA. [2] Graduate Program in Biochemistry, Cell and Molecular Biology Allied Program, Weill Cornell Medical College, New York, New York, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Shao
authors.affiliation: Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
authors.forename: Kathryn V
authors.initials: KV
authors.lastname: Anderson
authors.affiliation: 1] Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA. [2] Graduate Program in Neuroscience, Weill Cornell Medical College, New York, New York, USA. [3] Graduate Program in Biochemistry, Cell and Molecular Biology Allied Program, Weill Cornell Medical College, New York, New York, USA.
authors.forename: Song-Hai
authors.initials: SH
authors.lastname: Shi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000235:genetics; D002502:Centrioles / Q000235:genetics; D002540:Cerebral Cortex / Q000166:cytology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008938:Mitosis / Q000235:genetics; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000166:cytology*