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The Hippo pathway and p27Kip1 cooperate to suppress mitotic regeneration in the organ of Corti and the retina

Eva Jahanshir,Juan Llamas,Yeeun Kim,Kevin Biju,Sanyukta Oak,Ksenia Gnedeva

Published 2025 in Proceedings of the National Academy of Sciences of the United States of America

ABSTRACT

Significance Understanding the shared molecular mechanisms underlying mitotic quiescence in the auditory and visual sensory epithelia provides crucial insights for developing new therapeutic strategies for hair cell and photoreceptor regeneration. Our work reveals an antagonistic relationship between Yap, a key mitogen driving regeneration in tissues such as skin and intestine, and p27Kip1, a Cip/Kip family cell cycle kinase inhibitor. The unusual transcriptional control of Cdkn1b, which encodes p27Kip1, maintains high levels of this protein, preventing Yap-mediated cell cycle reentry and halting the regenerative response. Notably, when p27Kip1 levels are experimentally reduced, both supporting cells in the cochlea and Müller glia in the retina proliferate in response to Yap, producing progeny capable of sensory differentiation.

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