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Publication : Uncoordinated maturation of developing and regenerating postnatal mammalian vestibular hair cells.

First Author  Wang T Year  2019
Journal  PLoS Biol Volume  17
Issue  7 Pages  e3000326
PubMed ID  31260439 Mgi Jnum  J:277196
Mgi Id  MGI:6323062 Doi  10.1371/journal.pbio.3000326
Citation  Wang T, et al. (2019) Uncoordinated maturation of developing and regenerating postnatal mammalian vestibular hair cells. PLoS Biol 17(7):e3000326
abstractText  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.
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