Mcidas and GemC1/Lynkeas are key regulators for the generation of multiciliated ependymal cells in the adult neurogenic niche

Abstract

Multiciliated cells are abundant in the epithelial surface of different tissues, including cells lining the walls of the lateral ventricles in the brain and the airway epithelium. Their main role is to control fluid flow and thus defects in their differentiation were implicated in many human disorders such as hydrocephalus, accompanied by defects in adult neurogenesis and mucociliary disorder in the airway system. Here we show that Mcidas, which was mutated in human mucociliary clearance disorder and GemC1/Lynkeas, previously implicated in cell cycle progression, are key regulators of multiciliated ependymal cells generation in the brain. Overexpression and knock down experiments show that Mcidas and GemC1/Lynkeas are sufficient and necessary for cell fate commitment and differentiation of radial glial cells to multiciliated ependymal cells. Furthermore, we show that GemC1/Lynkeas and Mcidas operate in hierarchical order, upstream of Foxj1 and c-Myb transcription factors, known regulators of ependymal cell generation, while Notch signaling is inhibiting their function. Our results suggest that Mcidas and GemC1/Lynkeas are key players for the generation of multiciliated ependymal cells of the adult neurogenic niche.