2026-02-26 国立遺伝学研究所
dpy19l1ノックアウト変異体（右）は体軸が湾曲する。
＜関連情報＞
- https://www.nig.ac.jp/nig/ja/2026/02/research-highlights_ja/rh20260226.html
- https://www.sciencedirect.com/science/article/pii/S0006291X26002743
C -マンノシルトランスフェラーゼDpy19l1lは、ゼブラフィッシュにおいてSCO-スポンジンの分泌を介して体軸形成を制御する C-mannosyltransferase Dpy19l1l regulates body axis formation via secretion of SCO-spondin in zebrafish
Tomoko Usami, Takehiro Suzuki, Sayaka Okubo, Hiroki Kamo, Hajime Fukui, Naoshi Dohmae, Kazuhide Asakawa, Siro Simizu
Biochemical and Biophysical Research Communications Available online: 20 February 2026
DOI:https://doi.org/10.1016/j.bbrc.2026.153510
Highlights
- Zebrafish Dpy19l1l and Dpy19l3 catalyze substrate-specific C-mannosylation.
- Dpy19l1l and Dpy19l3 catalyze C-mannosylation of SCO-spondin.
- Dpy19l1l, but not Dpy19l3, regulates body axis formation in zebrafish.
Abstract
C-mannosylation is an evolutionarily conserved but poorly understood glycosylation process, particularly regarding its physiological roles and pathological relevance. Here, we propose that C-mannosylation plays a key role in maintaining body axis straightness during zebrafish embryogenesis. Using Drosophila S2 cells and mass spectrometry, we show that zebrafish Dpy19-like 1, like (Dpy19l1l) and Dpy19-like 3 (Dpy19l3) catalyze substrate-specific C-mannosylation. Knockout of dpy19l1l resulted in a scoliosis-like “curly tail down” phenotype, whereas dpy19l3 knockout showed no obvious abnormalities. Based on its consensus sequence and biological function, we identified the giant extracellular glycoprotein SCO-spondin as a candidate substrate of Dpy19l1l and confirmed its C-mannosylation by using S2 cells. Live imaging of transgenic zebrafish expressing GFP-tagged SCO-spondin revealed that in dpy19l1l mutants, SCO-spondin fails to be secreted into the cerebrospinal fluid and accumulates at the flexural organ and floor plate, resulting in the loss of the Reissner fiber. These findings uncover a novel in vivo function of C-mannosylation and provide new insights into the molecular pathogenesis of scoliosis.
