Retinoic acid degradation shapes zonal development of vestibular organs and sensitivity to transient linear accelerations

Authors

Kazuya Ono, National Institutes of Health
James Keller, National Institutes of Health & Qiagen Sciences Inc.
Omar López Ramírez, University of Chicago
Antonia González Garrido, University of Chicago
Omid A. Zobeiri, McGill University
Hui Ho Vanessa Chang, McGill University
Sherri M. Jones, University of Nebraska-LincolnFollow
Andrianna Ayiotis, Johns Hopkins University School of Medicine
Gregg Duester, Stanford Burnham Prebys Medical Discovery Institutes
Charles C. Della Santina, Johns Hopkins University School of Medicine & ohns Hopkins University School of Medicine
Sarath Vijayakumar, University of Nebraska-Lincoln
Kathleen E. Cullen, Johns Hopkins University School of Medicine
Ruth Anne Eatock, University of Chicago
Doris K. Wu, National Institutes of HealthFollow

ORCID IDs

http://orcid.org/0000-0002-3857-0055

http://orcid.org/0000-0002-5256-0013

http://orcid.org/0000-0003-2578-3155

http://orcid.org/0000-0002-5497-7197

http://orcid.org/0000-0003-4335-3650

http://orcid.org/0000-0001-5018-3659

http://orcid.org/0000-0002-9348-0933

http://orcid.org/0000-0001-7547-2051

Document Type

Article

Date of this Version

1-2-2020

Citation

2020 Author(s)

Comments

NATURE COMMUNICATIONS | (2020)11:63 | https://doi.org/10.1038/s41467-019-13710-4 | www.nature.com/naturecommunications

Abstract

Each vestibular sensory epithelium in the inner ear is divided morphologically and physio- logically into two zones, called the striola and extrastriola in otolith organ maculae, and the central and peripheral zones in semicircular canal cristae. We found that formation of striolar/central zones during embryogenesis requires Cytochrome P450 26b1 (Cyp26b1)- mediated degradation of retinoic acid (RA). In Cyp26b1 conditional knockout mice, formation of striolar/central zones is compromised, such that they resemble extrastriolar/peripheral zones in multiple features. Mutants have deficient vestibular evoked potential (VsEP) responses to jerk stimuli, head tremor and deficits in balance beam tests that are consistent with abnormal vestibular input, but normal vestibulo-ocular reflexes and apparently normal motor performance during swimming. Thus, degradation of RA during embryogenesis is required for formation of highly specialized regions of the vestibular sensory epithelia with specific functions in detecting head motions.