Repair of surviving hair cells in the damaged mouse utricle

Proc Natl Acad Sci U S A. 2022 Apr 12;119(15):e2116973119. doi: 10.1073/pnas.2116973119. Epub 2022 Apr 5.

Abstract

Sensory hair cells (HCs) in the utricle are mechanoreceptors required to detect linear acceleration. After damage, the mammalian utricle partially restores the HC population and organ function, although regenerated HCs are primarily type II and immature. Whether native, surviving HCs can repair and contribute to this recovery is unclear. Here, we generated the Pou4f3DTR/+; Atoh1CreERTM/+; Rosa26RtdTomato/+ mouse to fate map HCs prior to ablation. After HC ablation, vestibular evoked potentials were abolished in all animals, with ∼57% later recovering responses. Relative to nonrecovery mice, recovery animals harbored more Atoh1-tdTomato+ surviving HCs. In both groups, surviving HCs displayed markers of both type I and type II subtypes and afferent synapses, despite distorted lamination and morphology. Surviving type II HCs remained innervated in both groups, whereas surviving type I HCs first lacked and later regained calyces in the recovery, but not the nonrecovery, group. Finally, surviving HCs initially displayed immature and subsequently mature-appearing bundles in the recovery group. These results demonstrate that surviving HCs are capable of self-repair and may contribute to the recovery of vestibular function.

Keywords: hair cell; regeneration; repair; utricle; vestibular.

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Cell Survival / genetics
  • Hair Cells, Vestibular* / physiology
  • Homeodomain Proteins / genetics
  • Mice
  • Mice, Mutant Strains
  • RNA, Untranslated / genetics
  • Regeneration* / genetics
  • Saccule and Utricle* / cytology
  • Saccule and Utricle* / injuries
  • Saccule and Utricle* / physiology
  • Transcription Factor Brn-3C / genetics

Substances

  • Atoh1 protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • Gt(ROSA)26Sor non-coding RNA, mouse
  • Homeodomain Proteins
  • Pou4f3 protein, mouse
  • RNA, Untranslated
  • Transcription Factor Brn-3C