Uncoordinated maturation of developing and regenerating postnatal mammalian vestibular hair cells

Authors

Tian Wang, Stanford University School of Medicine
Mamiko Niwa, Stanford University School of Medicine
Zahra N. Sayyid, Stanford University School of Medicine
Davood K. Hosseini, Stanford University School of Medicine
Nicole Pham, Stanford University School of Medicine
Sherri M. Jones, University of Nebraska-LincolnFollow
Anthony J. Ricci, Stanford University School of MedicineFollow
Alan G. Cheng, Stanford University School of MedicineFollow

ORCID IDs

Tian Wang http://orcid.org/0000-0002-5249-4896

Mamiko Niwa http://orcid.org/0000-0003-1353-3394

Davood K. Hosseini http://orcid.org/0000-0002-0393-8016

Nicole Pham http://orcid.org/0000-0001-6719-3159

Anthony J. Ricci http://orcid.org/0000-0002-1706-8904

Alan G. Cheng http://orcid.org/0000-0002-4702-8401

Document Type

Article

Date of this Version

7-1-2019

Citation

Wang T, Niwa M, Sayyid ZN, Hosseini DK, Pham N, Jones SM, et al. (2019) Uncoordinated maturation of developing and regenerating postnatal mammalian vestibular hair cells. PLoS Biol 17(7): e3000326. https://doi.org/10.1371/ journal.pbio.3000326

Comments

Copyright: © 2019 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License,

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.