Hippo-YAP/TAZ signaling in inner ear development, injury, and regeneration: evidence synthesis and the biomechanical brake hypothesis

Sensorineural hearing loss in mammals is essentially irreversible. Mature cochlear hair cells, once lost, do not regenerate. Non-mammalian vertebrates retain this ability, but in the mammalian organ of Corti, supporting cells lose their proliferative and transdifferentiation competence after birth. Reactivation of classical developmental pathways has also shown limited success in the adult cochlea....

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No actionable clinical change — this is basic science research proposing a mechanistic hypothesis; findings are far from clinical translation but are relevant to researchers working on hair cell regeneration therapies.

Understanding why mammalian cochlear hair cells fail to regenerate is one of audiology's most critical unsolved problems; the biomechanical brake hypothesis offers a testable new framework that could guide future regenerative therapy research.

1. 01Reviews the role of Hippo-YAP/TAZ signaling — a pathway that regulates cell growth and mechanical sensing — in inner ear biology.
2. 02Proposes a novel 'biomechanical brake hypothesis' to explain why cochlear hair cells do not regenerate in mammals.
3. 03Synthesizes evidence from inner ear development, injury, and regeneration research.
4. 04Published in Frontiers in Cell and Developmental Biology (DOI: 10.3389/fcell.2026.1878367).
5. 05Findings are preclinical; no human or direct clinical data are presented.

PMID

42846680

DOI

10.3389/fcell.2026.1878367.

Journal

Frontiers in Cell and Developmental Biology

Publication type

review

Evidence level

5

Population

Preclinical models and published literature on inner ear development and regeneration

Intervention

Hippo-YAP/TAZ signaling pathway modulation in inner ear development and regeneration