Tian Guiyou, Huang Lirong, Xu Zhaopeng, Lu Chen, Yuan Wei, Wu Yulin, Liao Zhipeng, Gao Jia, Luo Qiang, Cheng Bo, Liao Xinjun, Lu Huiqiang
Jiangxi Provincial Key Laboratory of Synthetic Pharmaceutical Chemistry, School of Geography and Environmental Engineering, Gannan Normal University, Ganzhou 341000, China.
Affiliated Hospital of Jinggangshan University, College of Life Sciences, Jinggangshan University, Ji'an 343000, Jiangxi, China.
Sci Adv. 2025 May 9;11(19):eadv2032. doi: 10.1126/sciadv.adv2032.
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 (dumpy-19 like 1 like) is expressed in the spinal cord during zebrafish embryonic development. Mutation in resulted in idiopathic scoliosis (IS)-like body axis curvature in the absence of muscle or cilia defects. URP2 expression was down-regulated in mutants. Notably, RF formation was impaired in mutants, and a similar phenotype was induced in wild-type embryos by injecting messenger RNA encoding a C-mannosylation catalytic site-mutated variant (E106A ). 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.
连合下器官（SCO）-脊髓素的成功分泌和组装对于斑马鱼中雷斯纳纤维（RF）的形成和体轴伸直至关重要。然而，RF形成的潜在机制在很大程度上仍然未知。在此，我们报告C-甘露糖基转移酶（类dumpy-19样1）在斑马鱼胚胎发育期间在脊髓中表达。其突变在没有肌肉或纤毛缺陷的情况下导致特发性脊柱侧凸（IS）样体轴弯曲。URP2在突变体中表达下调。值得注意的是，RF形成在突变体中受损，并且通过注射编码C-甘露糖基化催化位点突变的变体（E106A）的信使RNA在野生型胚胎中诱导出类似的表型。此外，E106A mDPY19L1L未能糖基化Flag标签的SCO-脊髓素TSRs（血小板反应蛋白1型重复序列）。我们的研究结果表明，DPY19L1L介导的SCO-脊髓素TSRs的C-甘露糖基化促进RF形成和URP2诱导，代表了斑马鱼体轴伸直的关键补充机制。
