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 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, plays 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 hpf, in the midbrain/hindbrain boundary, the brainstem and the pre-neuromast of lateral line at 48 hpf in a strict spatiotemporal regulation. Both up- and down-regulation 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 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 up-regulated proapoptotic gene zBax2 and down-regulated prosurvival gene zMcl1b; in contrast, the level of zBax2 was decreased and of zMcl1b enhanced by miles-apart overexpression. Collectively, miles-apart 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 organegenesis. At larva stage miles-apart as an upstream regulator of bcl-2 gene family, plays a role in protection of hair cells against apoptosis by promoting expression of prosurvival gene zMcl1b and suppressing proapoptotic gene zBax2.