Multiple supporting cell subtypes are capable of spontaneous hair cell regeneration in the neonatal mouse cochlea

Development. 2019 Feb 15;146(4):dev171009. doi: 10.1242/dev.171009.

Abstract

Supporting cells (SCs) are known to spontaneously regenerate hair cells (HCs) in the neonatal mouse cochlea, yet little is known about the relative contribution of distinct SC subtypes which differ in morphology and function. We have previously shown that HC regeneration is linked to Notch signaling, and some SC subtypes, but not others, lose expression of the Notch effector Hes5 Other work has demonstrated that Lgr5-positive SCs have an increased capacity to regenerate HCs; however, several SC subtypes express Lgr5. To further investigate the source for spontaneous HC regeneration, we used three CreER lines to fate-map distinct groups of SCs during regeneration. Fate-mapping either alone or combined with a mitotic tracer showed that pillar and Deiters' cells contributed more regenerated HCs overall. However, when normalized to the total fate-mapped population, pillar, Deiters', inner phalangeal and border cells had equal capacity to regenerate HCs, and all SC subtypes could divide after HC damage. Investigating the mechanisms that allow individual SC subtypes to regenerate HCs and the postnatal changes that occur in each group during maturation could lead to therapies for hearing loss.

Keywords: Deiters' cells; Fate-mapping; Inner phalangeal cells; Mitotic regeneration; Pillar cells; Supporting cell subtypes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cell Death
  • Cell Differentiation
  • Cell Lineage
  • Cell Proliferation
  • Cochlea / physiology*
  • Crosses, Genetic
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • Hair Cells, Auditory / physiology*
  • Hearing Loss
  • Integrases / metabolism
  • Labyrinth Supporting Cells / physiology*
  • Mice
  • Mice, Transgenic
  • Microscopy, Confocal
  • Mitosis
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, Notch / metabolism
  • Regeneration*
  • Repressor Proteins / metabolism
  • Signal Transduction

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Cdkn1b protein, mouse
  • Hes5 protein, mouse
  • Lgr5 protein, mouse
  • Receptors, G-Protein-Coupled
  • Receptors, Notch
  • Repressor Proteins
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cre recombinase
  • Integrases