The Hippo pathway and p27Kip1 cooperate to suppress sensory receptor regeneration in the organ of Corti and the retina.

The mammalian auditory sensory organ, the organ of Corti, has no capacity for regenerating lost hair cells, leading to permanent hearing impairment. In this study, we demonstrate that auditory supporting cells resist Yap activation after Hippo inhibition and uncover the molecular mechanism maintaining quiescence in the adult cochlear supporting cells. Overall design: Primary and cultured organs of Corti were dissociated into a single cell suspension and supporting cells were purified via fluorescence-activated cell sorting to prepare RNA-Seq libraries. For in vitro experiments, p1 organs of Corti were dissected from Lfng-eGFP mice and cultured in presence of DMSO or Lats Kinase inhibitor (LKI) for 5 days before profiling eGFP-positive supporting cells. For in vivo experiments, organs of Corti were dissected from P8 Lfng-CreERT2/Rosa26-LSL-tdT/Pou4f3-DTR mice, treated with tamoxifen at P2 to label supporting cells and treated with diphtheria toxin fat P4 to ablate hair cells. tdTomato-positive supporting cells with and without hair cell damage were profiled.