Loss of Mst1/2 activity promotes non-mitotic hair cell generation in the neonatal organ of Corti

Xiaoling Lu; Huiqian Yu; Jiaoyao Ma; Kunkun Wang; Luo Guo; Yanping Zhang; Boan Li; Zehang Zhao; Huawei Li; Shan Sun

doi:10.1038/s41536-022-00261-4

October 25, 2022npj Regenerative MedicineOpen Access

Loss of Mst1/2 activity promotes non-mitotic hair cell generation in the neonatal organ of Corti

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Key Points

To investigate the role of the Hippo signaling pathway in sensory hair cell damage and regeneration in the mammalian neonatal organ of Corti.
Performed in vitro RNA-sequencing on cochlear tissue to profile pathway changes during hair cell damage and self-repair.
Manipulated Hippo signaling through pharmacological or genetic Mst1/2 inhibition and Yap overexpression in neonatal supporting cells.
Evaluated synergy with the Notch pathway and assessed regenerated hair cell maturation, cilia morphology, and neural connections in vivo.
Inhibition of Mst1/2 or overexpression of Yap stimulated YAP nuclear accumulation primarily in supporting cells, driving supernumerary hair cell production and regeneration post-injury.
Hippo signaling worked synergistically with the Notch pathway to promote non-mitotic hair cell conversion.
Regenerated hair cells expressed classic hair cell markers, developed functional cilia structures, and successfully established neural connections to auditory regions in vivo.

Implication

Laboratory study demonstrates hair cell regeneration in neonatal cochlear tissue via Hippo pathway inhibition, suggesting therapeutic targets for hearing loss.

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Cite This Study

Lu et al. (2022) studied this question.

synapsesocial.com/papers/6aaf375cc5a6748b3a77556e https://doi.org/10.1038/s41536-022-00261-4

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Loss of Mst1/2 activity promotes non-mitotic hair cell generation in the neonatal organ of Corti

Key Points

Implication

Discussion

Cite This Study

Loss of Mst1/2 activity promotes non-mitotic hair cell generation in the neonatal organ of Corti

Key Points

Implication

Discussion

Cite This Study

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