Uncoordinated maturation of developing and regenerating postnatal mammalian vestibular hair cells

Citations Over TimeTop 10% of 2019 papers

Abstract

Sensory hair cells are mechanoreceptors required for hearing and balance functions. From embryonic development, hair cells acquire apical stereociliary bundles for mechanosensation, basolateral ion channels that shape receptor potential, and synaptic contacts for conveying information centrally. These key maturation steps are sequential and presumed coupled; however, whether hair cells emerging postnatally mature similarly is unknown. Here, we show that in vivo postnatally generated and regenerated hair cells in the utricle, a vestibular organ detecting linear acceleration, acquired some mature somatic features but hair bundles appeared nonfunctional and short. The utricle consists of two hair cell subtypes with distinct morphological, electrophysiological and synaptic features. In both the undamaged and damaged utricle, fate-mapping and electrophysiology experiments showed that Plp1+ supporting cells took on type II hair cell properties based on molecular markers, basolateral conductances and synaptic properties yet stereociliary bundles were absent, or small and nonfunctional. By contrast, Lgr5+ supporting cells regenerated hair cells with type I and II properties, representing a distinct hair cell precursor subtype. Lastly, direct physiological measurements showed that utricular function abolished by damage was partially regained during regeneration. Together, our data reveal a previously unrecognized aberrant maturation program for hair cells generated and regenerated postnatally and may have broad implications for inner ear regenerative therapies.

Related Papers

• → Hair cell morphological patterns and polarity organization in the sea lamprey vestibular cristae(2023)4 cited
• → Differences Between Stereocilia Numbers on Type I and Type II Vestibular Hair Cells(2004)41 cited
• [Scanning electron microscopic observation of human vestibular sensory epithelia].(1995)
• → Live imaging of hair bundle polarity acquisition in the mouse utricle demonstrates a critical timeline for transcription factor Emx2(2020)
• → The sensory epithelium of the crista(1983)