The glucose-sensing Mondo pathway regulates expression of metabolic genes in mammals. Here, we characterized its function in the zebrafish and revealed an unexpected role of this pathway in vertebrate embryonic development. We showed that knockdown of mondoa impaired the early morphogenetic movement of epiboly in zebrafish embryos and caused microtubule defects. Expression of genes in the terpenoid backbone and sterol biosynthesis pathways upstream of pregnenolone synthesis was coordinately downregulated in these embryos, including the most downregulated gene nsdhl. Loss of Nsdhl function likewise impaired epiboly, similar to MondoA loss of function. Both epiboly and microtubule defects were partially restored by pregnenolone treatment. Maternal-zygotic mutants of mondoa showed perturbed epiboly with low penetrance and compensatory changes in the expression of terpenoid/sterol/steroid metabolism genes. Collectively, our results show a novel role for MondoA in the regulation of early vertebrate development, connecting glucose, cholesterol and steroid hormone metabolism with early embryonic cell movements.

中文翻译：

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MondoA 调节斑马鱼表皮代谢所需的胆固醇生物合成相关途径的基因表达

葡萄糖感应 Mondo 途径调节哺乳动物代谢基因的表达。在这里，我们描述了它在斑马鱼中的功能，并揭示了该途径在脊椎动物胚胎发育中的意想不到的作用。我们发现，蒙多亚的敲低会损害斑马鱼胚胎中表皮的早期形态发生运动，并导致微管缺陷。在这些胚胎中，萜类主链和孕烯醇酮合成上游的甾醇生物合成途径中的基因表达协同下调，包括下调幅度最大的基因 nsdhl。Nsdhl 功能的丧失同样会损害表观代谢，类似于 MondoA 功能的丧失。孕烯醇酮治疗可部分恢复外延和微管缺陷。蒙多亚的母本合子突变体表现出外显率低的扰动以及萜类/甾醇/类固醇代谢基因表达的补偿性变化。总的来说，我们的结果表明 MondoA 在调节早期脊椎动物发育中发挥着新作用，将葡萄糖、胆固醇和类固醇激素代谢与早期胚胎细胞运动联系起来。