The final size and function of the adult central nervous system (CNS) is determined by neuronal lineages generated by neural stem cells (NSCs) in the developing brain. In Drosophila, NSCs called neuroblasts (NBs) reside within a specialised microenvironment called the glial niche. Here, we explore non-autonomous glial regulation of NB proliferation. We show that lipid droplets (LDs) which reside within the glial niche are closely associated with the signalling molecule Hedgehog (Hh). Under physiological conditions, cortex glial Hh is autonomously required to sustain niche chamber formation, and non-autonomously restrained to prevent ectopic Hh signalling in the NBs. In the context of cortex glial overgrowth, induced by Fibroblast Growth Factor (FGF) activation, Hh and lipid storage regulators Lsd-2 and Fasn1 were upregulated, resulting in activation of Hh signalling in the NBs; which in turn disrupted NB cell cycle progression and reduced neuronal production. We show that the LD regulator Lsd-2 modulates Hh's ability to signal to NBs, and de novo lipogenesis gene Fasn1 regulates Hh post-translational modification via palmitoylation. Together, our data suggest that the glial niche non-autonomously regulates NB proliferation and neural lineage size via Hh signaling that is modulated by lipid metabolism genes.

中文翻译：

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胶质刺猬和脂质代谢调节果蝇的神经干细胞增殖。

成人中枢神经系统（CNS）的最终大小和功能取决于发育中的大脑中神经干细胞（NSC）产生的神经元谱系。在果蝇中，称为神经母细胞（NBs）的NSC驻留在称为神经胶质小生境的特殊微环境中。在这里，我们探讨了NB增殖的非自主神经胶质调节。我们显示，位于神经胶质生态位内的脂滴（LDs）与信号分子刺猬（Hh）紧密相关。在生理条件下，皮层神经胶质Hh是自主维持小生境腔形成所必需的，非自主地是为了防止NB中的异位Hh信号传导。在由成纤维细胞生长因子（FGF）激活诱导的皮质神经胶质过度生长的背景下，Hh和脂质存储调节因子Lsd-2和Fasn1被上调，导致NB中Hh信号的激活；反过来会破坏NB细胞周期进程并减少神经元产生。我们表明，LD调节剂Lsd-2调节Hh向NBs发出信号的能力，并且从头脂肪生成基因Fasn1通过棕榈酰化调节Hh翻译后修饰。在一起，我们的数据表明，神经胶质生态位通过脂质代谢基因调节的Hh信号非自主地调节NB增殖和神经谱系大小。