N6-methyladenosine (m6A) is the most prevalent internal RNA modification, and has a widespread impact on mRNA stability and translation. Methyltransferase-like 3 (Mettl3) is a responsible methyltransferase for RNA m6A modification, and it is essential for early embryogenesis before or during gastrulation in mice and zebrafish. However, due to the early embryonic lethality, loss of function phenotypes of Mettl3 beyond gastrulation, especially during neurulation stages when spatial neural patterning takes place, remains elusive. Here, we address multiple roles of Mettl3 during Xenopus neurulation on the anteroposterior neural patterning, neural crest specification and neuronal cell differentiation. Knockdown of Mettl3 causes anteriorization of neurula and tailbud embryos along with the loss of neural crest and neuronal cells. Knockdown of the m6A reader Ythdf1 and mRNA degradation factors, such as 3’ to 5’ exonuclease complex component Lsm1 or mRNA uridylation enzyme Tut7, also show a similar neural patterning defects, suggesting that m6A-dependent mRNA destabilization regulates spatial neural patterning in Xenopus. We also address that canonical WNT signaling is inhibited in Mettl3 morphants, which may underlie the neural patterning defects of the morphants. Altogether, this study reveals functions of Mettl3 during spatial neural patterning in Xenopus.

中文翻译：

---

RNA m6A甲基转移酶Mettl3调节非洲爪蟾的空间神经模式

N6-甲基腺苷 (m6A) 是最普遍的内部 RNA 修饰，对 mRNA 稳定性和翻译具有广泛的影响。甲基转移酶样 3 (Mettl3) 是一种负责 RNA m6A 修饰的甲基转移酶，它对于小鼠和斑马鱼原肠胚形成之前或期间的早期胚胎发生至关重要。然而，由于早期胚胎致死率，Mettl3 在原肠胚形成后功能表型的丧失，特别是在发生空间神经模式的神经发育阶段，仍然难以捉摸。在这里，我们解决了 Mettl3 在非洲爪蟾中的多种作用对前后神经模式、神经嵴规范和神经元细胞分化的神经调节。Mettl3 的敲低导致神经元和尾芽胚胎的前化以及神经嵴和神经元细胞的损失。敲除 m6A 阅读器 Ythdf1 和 mRNA 降解因子，例如 3' 到 5' 外切核酸酶复合物成分 Lsm1 或 mRNA 尿苷化酶 Tut7，也显示出类似的神经模式缺陷，表明 m6A 依赖性 mRNA 失稳调节了非洲爪蟾的空间神经模式。我们还解决了 Mettl3 morphants 中典型的 WNT 信号传导受到抑制的问题，这可能是 morphants 神经模式缺陷的基础。总之，这项研究揭示了 Mettl3 在非洲爪蟾空间神经模式中的功能。