Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan.
Sci Rep. 2022 Jan 7;12(1):292. doi: 10.1038/s41598-021-04474-3.
Neurogenesis in the Drosophila central brain progresses dynamically in order to generate appropriate numbers of neurons during different stages of development. Thus, a central challenge in neurobiology is to reveal the molecular and genetic mechanisms of neurogenesis timing. Here, we found that neurogenesis is significantly impaired when a novel mutation, Nuwa, is induced at early but not late larval stages. Intriguingly, when the Nuwa mutation is induced in neuroblasts of olfactory projection neurons (PNs) at the embryonic stage, embryonic-born PNs are generated, but larval-born PNs of the same origin fail to be produced. Through molecular characterization and transgenic rescue experiments, we determined that Nuwa is a loss-of-function mutation in Drosophila septin interacting protein 1 (sip1). Furthermore, we found that SIP1 expression is enriched in neuroblasts, and RNAi knockdown of sip1 using a neuroblast driver results in formation of small and aberrant brains. Finally, full-length SIP1 protein and truncated SIP1 proteins lacking either the N- or C-terminus display different subcellular localization patterns, and only full-length SIP1 can rescue the Nuwa-associated neurogenesis defect. Taken together, these results suggest that SIP1 acts as a crucial factor for specific neurogenesis programs in the early developing larval brain.
果蝇中枢神经系统中的神经发生是动态进行的，以便在不同的发育阶段产生适当数量的神经元。因此，神经生物学的一个主要挑战是揭示神经发生时间的分子和遗传机制。在这里，我们发现当在早期而不是晚期幼虫阶段诱导新的突变 Nuwa 时，神经发生会显著受损。有趣的是，当在胚胎阶段的嗅觉投射神经元 (PN) 的神经母细胞中诱导 Nuwa 突变时，会产生胚胎起源的 PNs，但相同来源的幼虫起源的 PNs 则无法产生。通过分子特征分析和转基因拯救实验，我们确定 Nuwa 是果蝇 septin 相互作用蛋白 1 (sip1) 的功能丧失突变。此外，我们发现 SIP1 在神经母细胞中表达丰富，使用神经母细胞驱动子进行 sip1 的 RNAi 敲低会导致小而异常的大脑形成。最后，全长 SIP1 蛋白和缺失 N-或 C-末端的截断 SIP1 蛋白显示出不同的亚细胞定位模式，只有全长 SIP1 可以拯救与 Nuwa 相关的神经发生缺陷。综上所述，这些结果表明 SIP1 作为早期发育幼虫大脑中特定神经发生程序的关键因素发挥作用。
