N6‐methyladenosine (m⁶A) regulates a variety of physiological processes through modulation of RNA metabolism. This modification is particularly enriched in the nervous system of several species, and its dysregulation has been associated with neurodevelopmental defects and neural dysfunctions. In Drosophila, loss of m⁶A alters fly behavior, albeit the underlying molecular mechanism and the role of m⁶A during nervous system development have remained elusive. Here we find that impairment of the m⁶A pathway leads to axonal overgrowth and misguidance at larval neuromuscular junctions as well as in the adult mushroom bodies. We identify Ythdf as the main m⁶A reader in the nervous system, being required to limit axonal growth. Mechanistically, we show that the m⁶A reader Ythdf directly interacts with Fmr1, the fly homolog of Fragile X mental retardation RNA binding protein (FMRP), to inhibit the translation of key transcripts involved in axonal growth regulation. Altogether, this study demonstrates that the m⁶A pathway controls development of the nervous system and modulates Fmr1 target transcript selection.

中文翻译：

---

Ythdf 是一种 N6-甲基腺苷读取器，可调节 Fmr1 目标 mRNA 选择并限制果蝇中的轴突生长

N6-甲基腺苷 (m ⁶ A) 通过调节 RNA 代谢来调节多种生理过程。这种修饰在几个物种的神经系统中特别丰富，其失调与神经发育缺陷和神经功能障碍有关。在果蝇中，m ⁶ A 的损失会改变苍蝇的行为，尽管潜在的分子机制和 m ⁶ A 在神经系统发育过程中的作用仍然难以捉摸。在这里，我们发现 m ⁶ A 通路的损伤导致轴突过度生长和幼虫神经肌肉接头处以及成年蘑菇体的误导。我们将 Ythdf 确定为主要的 m ⁶神经系统中的阅读器，需要限制轴突生长。在机制上，我们表明 m ⁶ A 阅读器 Ythdf 直接与 Fmr1（脆性 X 智力低下 RNA 结合蛋白 (FMRP) 的苍蝇同源物）相互作用，以抑制参与轴突生长调节的关键转录本的翻译。总之，这项研究表明 m ⁶ A 通路控制神经系统的发育并调节 Fmr1 目标转录物的选择。