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Publication : Cortical neurogenesis in the absence of centrioles.

First Author  Insolera R Year  2014
Journal  Nat Neurosci Volume  17
Issue  11 Pages  1528-35
PubMed ID  25282615 Mgi Jnum  J:219422
Mgi Id  MGI:5620818 Doi  10.1038/nn.3831
Citation  Insolera R, et al. (2014) Cortical neurogenesis in the absence of centrioles. Nat Neurosci 17(11):1528-35
abstractText  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.
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