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Background  IK is a splicing factor that promotes spliceosome activation and contributes to pre-mRNA splicing. Although the molecular mechanism of IK has been previously reported in vitro, the physiological role of IK has not been fully understood in any animal model. Here, we generate an  ik  knock-out (KO) zebrafish using the CRISPR/Cas9 system to investigate the physiological roles of IK in vivo.    Results  The  ik  KO embryos display severe pleiotropic phenotypes, implying an essential role of IK in embryonic development in vertebrates. RNA-seq analysis reveals downregulation of genes involved in skeletal muscle differentiation in  ik  KO embryos, and there exist genes having improper pre-mRNA splicing among downregulated genes. The  ik  KO embryos display impaired neuromuscular junction (NMJ) and fast-twitch muscle development. Depletion of  ik  reduces  myod1 e xpression and upregulates  pax7a , preventing normal fast muscle development in a non-cell-autonomous manner. Moreover, when differentiation is induced in IK-depleted C2C12 myoblasts, myoblasts show a reduced ability to form myotubes. However, inhibition of IK does not influence either muscle cell proliferation or apoptosis in zebrafish and C2C12 cells.    Conclusion  This study provides that the splicing factor IK contributes to normal skeletal muscle development in vivo and myogenic differentiation in vitro .Supplementary Information  The online version contains supplementary material available at 10.1186/s12915-021-00980-y.

Loss of splicing factor IK impairs normal skeletal muscle development