Zmynd10 drives centriole biogenesis and multiciliogenesis through the transcriptional regulation of E2f4

Multiciliated cells (MCCs) play a crucial role in various physiological processes, including cerebrospinal fluid flow, mucus clearance, and reproductive transport, by coordinating ciliary movement. Their differentiation is regulated by the Notch signaling pathway, along with its downstream targets, Gemc1 and Mcidas transcription factors. This study focuses on Zmynd10, a dynein axonemal assembly factor, to investigate its molecular mechanisms that regulate polycilia differentiation. By constructing a model of Zmynd10-specific knockdown in mouse ependymal cells (mEPCs), we found that Zmynd10 knockdown resulted in a decrease in ciliary density and significantly downregulated the mRNA and protein expression of E2f4 and Deup1. Further experiments demonstrated that E2f4 knockdown inhibited Deup1 expression and reduced cilia numbers, while Zmynd10 regulated the E2f4-Deup1 axis by activating the E2f4 promoter. This study reveals for the first time that Zmynd10 drives centriole amplification through the transcriptional regulation of the E2f4-Deup1 pathway, providing new insights into the molecular mechanisms underlying multicilia differentiation.