RRC ID 88432
Author Ono K, Keller J, López Ramírez O, González Garrido A, Zobeiri OA, Chang HHV, Vijayakumar S, Ayiotis A, Duester G, Della Santina CC, Jones SM, Cullen KE, Eatock RA, Wu DK.
Title Retinoic acid degradation shapes zonal development of vestibular organs and sensitivity to transient linear accelerations.
Journal Nat Commun
Abstract 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.
Volume 11(1)
Pages 63
Published 2020-1-2
DOI 10.1038/s41467-019-13710-4
PII 10.1038/s41467-019-13710-4
PMID 31896743
PMC PMC6940366
MeSH Animals Evoked Potentials / genetics Evoked Potentials / physiology Female Gene Expression Regulation, Developmental Head / physiopathology Mice, Inbred C57BL Mice, Knockout Osteopontin / metabolism Otolithic Membrane / cytology Otolithic Membrane / embryology* Otolithic Membrane / metabolism Retinal Dehydrogenase / genetics Retinal Dehydrogenase / metabolism Retinoic Acid 4-Hydroxylase / genetics Retinoic Acid 4-Hydroxylase / metabolism* Saccule and Utricle / cytology Saccule and Utricle / embryology Tremor / genetics Tremor / physiopathology Tretinoin / metabolism* Vestibular Function Tests Vestibule, Labyrinth / embryology Vestibule, Labyrinth / metabolism
IF 12.121
Resource
Mice RBRC04333