TY - JOUR
T1 - Retinoic acid degradation shapes zonal development of vestibular organs and sensitivity to transient linear accelerations
AU - Ono, Kazuya
AU - Keller, James
AU - López Ramírez, Omar
AU - González Garrido, Antonia
AU - Zobeiri, Omid A.
AU - Chang, Hui Ho Vanessa
AU - Vijayakumar, Sarath
AU - Ayiotis, Andrianna
AU - Duester, Gregg
AU - Della Santina, Charles C.
AU - Jones, Sherri M.
AU - Cullen, Kathleen E.
AU - Eatock, Ruth Anne
AU - Wu, Doris K.
N1 - Publisher Copyright:
© 2020, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Each vestibular sensory epithelium in the inner ear is divided morphologically and physiologically 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.
AB - Each vestibular sensory epithelium in the inner ear is divided morphologically and physiologically 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.
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U2 - 10.1038/s41467-019-13710-4
DO - 10.1038/s41467-019-13710-4
M3 - Article
C2 - 31896743
AN - SCOPUS:85077473893
SN - 2041-1723
VL - 11
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 63
ER -