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Phenotypes

Mouse phenotype:

microphthalmia, male infertility, abnormal cranium morphology, female infertility

Subcellular localization

Ciliary associated gene, Nucleoplasm, Nuclear membrane, Nucleoli, Cytosol

Functional category

• Ciliary assembly/disassembly

Function

CDK4 and CDK6 activity are required to initiate multiciliated cell differentiation by promoting the transition from the G1/G0-like phase to the S-like phase of the multiciliation cycle. Inhibition of CDK4/6 blocked centriole amplification, ciliogenesis, and expression of key multiciliogenesis regulators such as MYB and FOXJ1. CDK4/6 inhibition also reduced expression of early multiciliated cell differentiation genes, including GMNC, MYCL, MYB, and FOXJ1. Conversely, overexpression of Cyclin D1 promoted multiciliated cell formation, indicating that Cyclin D1–CDK4/6 signaling drives the initiation of multiciliogenesis and ciliogenesis (38811726).