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.
Highlights
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
As the sensory epithelium matures, Aldh1a3 immunoreactivity is localized to both hair cells (HCs) and supporting cells (SCs) in the extrastriola and some HCs in the striola by postnatal day 0 (P0) (Supplementary Fig. 2)
In Aldh1a3−/− mice, the calbindin-expressing domain is increased in the utricle but not in the lateral crista (Fig. 2i, n, o, Table 1), consistent with the expanded striolar region in the Aldh1a3−/− mutants. These results suggest that formation of the striolar/central zone in the vestibular organs requires Cytochrome P450 26b1 (Cyp26b1) enzyme to degrade the retinoic acid (RA) emanating from the surrounding sensory tissue, which is largely generated by Aldh1a3 in the maculae, not in the cristae (Table 1)
Summary
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 show that Cyp26b1 conditional knockout (cKO) mice exhibit a severe reduction of striolar/central zones as manifested by a number of morphological, molecular, and physiological properties These mice have normal horizontal angular vestibular-ocular reflexes (aVOR), driven by horizontal canal cristae, and normal responses to off-vertical axis rotation (OVAR), driven by the macular organs, but they lack VsEP and have head tremor and deficits during balance beam tests. These results suggest that striolas and central zones are not essential for mediating VORs, but are important for responding to changes in linear acceleration and are likely important for controlling head stability and performing challenging vestibulomotor activities
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