Spatiotemporal differences in otoconial gene expression

Abstract

Otoconia are minute bio-crystals composed of glycoproteins, proteoglycans and CaCO3, and are indispensable for sensory processing in the utricle and saccule. Otoconia abnormalities and degeneration can cause or facilitate crystal dislocation to the ampulla, leading to vertigo and imbalance in humans. In order to better understand the molecular mechanism controlling otoconia formation and maintenance, we have examined the spatial and temporal expression differences of otoconial genes in the mouse inner ear at developmental, mature and aging stages using whole transcriptome sequencing (RNA-Seq) and quantitative RT-PCR. We show that the expression levels of most otoconial genes are much higher in the utricle and saccule compared to other inner ear tissues before postnatal stages in C57Bl/6J mice, and the expression of a few of these genes is restricted to the embryonic utricle and saccule. After the early postnatal stages, expression of all otoconial genes in the utricle and saccule is drastically reduced, while a few genes gain expression dominance in the aging ampulla, indicating a potential for ectopic debris formation in the latter tissue at old ages. The data suggest that the expression of otoconial genes is tightly regulated spatially and temporally during developmental stages and can become unregulated at aging stages.

Functional derivatives of human dentin matrix protein 1 modulate morphology of calcium carbonate crystals

“…Recently, expression of DMP1 was detected in the murine inner ear. The expression level was significantly higher in the utricle and saccule than in cochlea . DMP1 was also found in murine otoconia .…”

“…Studies of both the mouse and zebrafish model systems help to define how human otoconia form . As concentration of calcium ions is low (in the order of 0.1 mM), protein activity seems to be required for crystal seeding and growth . The organic components of otoconia are either the same or belong to the same family as bone matrix proteins, however, the expression levels are different and their roles in the crystal formation remain unclear.…”

“…OPN is a good example. The protein is highly expressed in utricle and saccule . OPN have long been known to be highly expressed by osteoblasts and osteoclasts.…”

Cadmium Disrupts Vestibular Function by Interfering with Otolith Formation

“…Zebrafish ( Danio rerio ) have become an increasingly valuable vertebrate model system in toxicology 41,15 due to their high fecundity, external and transparent development, rapid generational times, reliance on evolutionarily conserved developmental regulatory gene networks, and sequenced genome, which facilitates mechanism-based toxicity studies. Like all vertebrate organisms, zebrafish have structural and sensory apparatus to perceive gravitational and positional cues for spatial awareness and posture control 16 , and perceive gravity and linear acceleration using mineralized biocrystals coupled to hair cells within the inner ear in a manner similar to other vertebrates, including humans. 16 In zebrafish, these biocrystals are consolidated into three distinct and large structures termed otoliths that each directly interact with an entire patch of sensory epithelium located in the saccule, utricle, and a non-mammalian specific otolithic region known as the lagena 6 .…”

“…Like all vertebrate organisms, zebrafish have structural and sensory apparatus to perceive gravitational and positional cues for spatial awareness and posture control 16 , and perceive gravity and linear acceleration using mineralized biocrystals coupled to hair cells within the inner ear in a manner similar to other vertebrates, including humans. 16 In zebrafish, these biocrystals are consolidated into three distinct and large structures termed otoliths that each directly interact with an entire patch of sensory epithelium located in the saccule, utricle, and a non-mammalian specific otolithic region known as the lagena 6 . The formation of otoliths in zebrafish has not yet been completely characterized but studies in trout and other species have shown that daily variations in the composition of vestibular endolymph are required 8,9 .…”