MicroRNA-1 affects the development of the neural crest and craniofacial skeleton via the mitochondrial apoptosis pathway

The neural crest is one of the key features of craniofacial development. MicroRNA-1 (miR-1) is a single-stranded noncoding RNA that serves an important role in embryonic development. However, the function of miR-1 in neural crest cells (NCCs) is unknown. Therefore, to evaluate the role of miR-1 in NCC development, a miR-1 mutant zebrafish was generated in the current study. Mouse NCCs were isolated from the first branchial arch of embryos at gestational day E9.5, and miR-1 was silenced using a miR-1 inhibitor. To the best of our knowledge, the present study was the first to report that homozygous zebrafish lacking miR-1 exhibited developmental defects in NCC-derived craniofacial bones, heart, melanocytes and iridophores. These defects may be caused by an increase in apoptosis of NCCs during their migration and differentiation in embryonic development. Moreover, the apoptosis analysis and western blotting results demonstrated that this effect was modulated via the mitochondrial apoptosis pathway, and miR-1 inhibited NCC apoptosis by modulating this pathway. These results collectively suggested that miR-1 in NCCs may be essential for craniofacial development.