DNA Damage-p53/P21 Response Contributes to Ependymal Cell Development

Abstract

Multiciliated Ependymal Cells and Adult Neural Stem Cells are components of the adult neurogenic niche, essential for brain homeostasis. These cells share a common glial cell lineage regulated by the Geminin family members Geminin and GemC1/Mcidas. Ependymal precursors require GemC1/Mcidas expression to massively amplify centrioles and become multiciliated cells. Here we show that GemC1-dependent differentiation occurs mostly in cycling Radial Glial Cells, in which a DNA damage response, including replicative stress and dysfunctional telomeres, arrests the cell cycle after the G1/S restriction point due to the activation of the p53-p21 pathway, which contributes to centriole amplification. Telomerase expression in Radial Glial Cells impairs ependymal differentiation and favors the Neural Stem Cell fate.