In a screen for human kinases that regulate Xenopus laevis embryogenesis, we identified Nagk and other components of the UDP-GlcNAc glycosylation salvage pathway as regulators of anteroposterior patterning and Wnt signaling. We find that the salvage pathway does not affect other major embryonic signaling pathways (Fgf, TGFβ, Notch, or Shh), thereby demonstrating specificity for Wnt signaling. We show that the role of the salvage pathway in Wnt signaling is evolutionarily conserved in zebrafish and Drosophila. Finally, we show that GlcNAc is essential for the growth of intestinal enteroids, which are highly dependent on Wnt signaling for growth and maintenance. We propose that the Wnt pathway is sensitive to alterations in the glycosylation state of a cell and acts as a nutritional sensor in order to couple growth/proliferation with its metabolic status. We also propose that the clinical manifestations observed in congenital disorders of glycosylation (CDG) in humans may be due, in part, to their effects on Wnt signaling during development.

中文翻译：

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Nagk 和 UDP-GlcNAc 补救途径对 Wnt 信号的发育调控

在对调节非洲爪蟾胚胎发生的人类激酶的筛选中，我们确定了 Nagk 和 UDP-GlcNAc 糖基化补救途径的其他成分作为前后模式和 Wnt 信号传导的调节剂。我们发现补救途径不影响其他主要的胚胎信号通路（Fgf、TGFβ、Notch 或 Shh），从而证明了 Wnt 信号的特异性。我们表明，在斑马鱼和果蝇中，补救途径在 Wnt 信号传导中的作用在进化上是保守的。最后，我们表明 GlcNAc 对肠类肠体的生长至关重要，肠类物质的生长和维持高度依赖 Wnt 信号传导。我们提出 Wnt 通路对细胞糖基化状态的改变很敏感，并充当营养传感器，以便将生长/增殖与其代谢状态结合起来。我们还提出，在人类先天性糖基化 (CDG) 障碍中观察到的临床表现可能部分是由于它们在发育过程中对 Wnt 信号传导的影响。