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.