Talpid3-Mediated Centrosome Integrity Restrains Neural Progenitor Delamination to Sustain Neurogenesis by Stabilizing Adherens Junctions

Abstract

Summary: Neurogenesis in the developing neocortex relies on extensive mitosis of radial glial cells (RGCs) in the apical surface. The nuclear migration of epithelial-like RGCs is fundamentally important for proper mitosis, but how the apical processes of RGCs are anchored to ensure the nucleokinetic behavior of RGCs remains unclear. Here we find that Talpid3, related to Joubert syndrome, is localized to the mother centriole of RGCs and is required for their apical mitosis. Genetic silencing of Talpid3 causes abnormal RGC delamination and thereby impairs their interkinetic nuclear migration in both cell-autonomous and non-autonomous manners. Further analyses reveal that Talpid3 associates with Ninein to regulate microtubule organization and maintain the integrity of adherens junctions to anchor RGCs. Moreover, genetic ablation of Talpid3 results in synchronized, ectopic mitosis of neural progenitors and dysregulated neurogenesis. Our study provides an intriguing perspective for the non-ciliogenic role of centriolar proteins in mediating cortical neurogenesis.

Keywords

• centrosome
• neurogenesis
• adherens junctions
• interkinetic nuclear migration
• neural progenitor delamination
• Talpid3