ArticleCell death & disease2013
Gene miles-apart is required for formation of otic vesicle and hair cells in zebrafish.
Article in Cell death & disease, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 15 citations in OpenAlex.
- Chromosome-Level Genome Assembly of the Loach Goby Rhyacichthys aspro Offers Insights Into Gobioidei Evolution.Molecular ecology resources · 2025Article
- Small fish, big prospects: using zebrafish to unravel the mechanisms of hereditary hearing loss.Hearing research · 2020Article
- Water Waves to Sound Waves: Using Zebrafish to Explore Hair Cell Biology.Journal of the Association for Research in Otolaryngology : JARO · 2019Review
- The conserved p.Arg108 residue in S1PR2 (DFNB68) is fundamental for proper hearing: evidence from a consanguineous Iranian family.BMC medical genetics · 2018Article
- Autosomal-Recessive Hearing Impairment Due to Rare Missense Variants within S1PR2.American journal of human genetics · 2016Article
- Effects of acoustic levitation on the development of zebrafish, Danio rerio, embryos.Scientific reports · 2015Article
- Mechanisms of otoconia and otolith development.Developmental dynamics : an official publication of the American Association of Anatomists · 2015Review
- Sphingosine 1-phosphate signaling pathway in inner ear biology. New therapeutic strategies for hearing loss?Frontiers in aging neuroscience · 2015Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hearing loss is a serious burden to physical and mental health worldwide. Aberrant development and damage of hearing organs are recognized as the causes of hearing loss, the molecular mechanisms underlining these pathological processes remain elusive. Investigation of new molecular mechanisms involved in proliferation, differentiation, migration and maintenance of neuromast primordium and hair cells will contribute to better understanding of hearing loss pathology. This knowledge will enable the development of protective agents and mechanism study of drug ototoxicity. In this study, we demonstrate that the zebrafish gene miles-apart, a homolog of sphingosine-1-phosphate receptor 2 (s1pr2) in mammals, has an important role in the development of otic vesicle, neuromasts and survival of hair cells. Whole-mount in situ hybridization of embryos showed that miles-apart expression occurred mainly in the encephalic region and the somites at 24 h.p.f. (hour post fertilization), in the midbrain/hindbrain boundary, the brainstem and the pre-neuromast of lateral line at 48 h.p.f. in a strict spatiotemporal regulation. Both up- and downregulation of miles-apart led to abnormal otoliths and semicircular canals, excess or few hair cells and neuromasts, and their disarranged depositions in the lateral lines. Miles-apart (Mil) dysregulation also caused abnormal expression of hearing-associated genes, including hmx2, fgf3, fgf8a, foxi1, otop1, pax2.1 and tmieb during zebrafish organogenesis. Moreover, in larvae miles-apart gene knockdown significantly upregulated proapoptotic gene zBax2 and downregulated prosurvival gene zMcl1b; in contrast, the level of zBax2 was decreased and of zMcl1b enhanced by miles-apart overexpression. Collectively, Mil activity is linked to organization and number decision of hair cells within a neuromast, also to deposition of neuromasts and formation of otic vesicle during zebrafish organogenesis. At the larva stage, Mil as an upstream regulator of bcl-2 gene family has a role in protection of hair cells against apoptosis by promoting expression of prosurvival gene zMcl1b and suppressing proapoptotic gene zBax2.
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