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). Here, we examine the function of centrioles in RGPs during cortical neurogenesis in mice by conditional removal of SAS-4, a protein required for centriole biogenesis. SAS-4 deletion leads to a progressive loss of centrioles, accompanied by RGP detachment from the VZ. Delocalized RGPs do not become outer subventricular zone RGPs (oRGs). While remaining proliferative, ectopic RGPs, as well as those in the VZ with a centrosomal deficit exhibit prolonged mitosis, p53 up-regulation and apoptosis, resulting in neuronal loss and microcephaly. Simultaneous removal of p53 fully rescues RGP death and microcephaly, but not RGP delocalization and randomized mitotic spindle orientation. Our findings define centriolar functions in anchoring RGPs in the VZ and ensuring their efficient mitoses, and also reveal the remarkable adaptability of RGPs in the developing cortex.