C-mannosyltransferase DPY19L1L-mediated Reissner Fiber formation is critical for zebrafish (Danio rerio) body axis straightening

The successful secretion and assembly of subcommissural organ (SCO)–spondin are crucial for Reissner Fiber (RF) formation and body axis straightening in zebrafish. However, the mechanisms underlying RF formation remain largely unknown. Here, we report that the C-mannosyltransferase dpy19l1l (dumpy-19 like 1 like) is expressed in the spinal cord during zebrafish embryonic development. Mutation in dpy19l1l resulted in idiopathic scoliosis (IS)–like body axis curvature in the absence of muscle or cilia defects. URP2 expression was down-regulated in dpy19l1l^−/− mutants. Notably, RF formation was impaired in dpy19l1l^−/− mutants, and a similar phenotype was induced in wild-type embryos by injecting messenger RNA encoding a C-mannosylation catalytic site-mutated dpy19l1l variant (E106A mdpy19l1l). Furthermore, E106A mDPY19L1L failed to glycosylate Flag-tagged SCO-spondin TSRs (thrombospondin type 1 repeats). Our findings suggest that DPY19L1L-mediated C-mannosylation of SCO-spondin TSRs promotes RF formation and URP2 induction, representing a critical supplementary mechanism for body axis straightening in zebrafish.