The formation of a complex nervous system requires the coordinated action of progenitor cell proliferation, differentiation and maturation. The Drosophila postembryonic central nervous system provides a powerful model for dissecting the cellular and molecular mechanisms underpinning neurogenesis. We previously identified the conserved zinc finger/RING protein Unkempt (Unk) as a key temporal regulator of neuronal differentiation in the Drosophila developing eye and showed that Unk acts downstream of the mechanistic target of rapamycin (mTOR) pathway together with its binding partner Headcase (Hdc). Here we investigate the role of Unk in Drosophila postembryonic thoracic neurogenesis. The Drosophila central nervous system contains neural stem cells, called neuroblasts, and neural progenitors, known as ganglion mother cells (GMCs). Unk is highly expressed in the central brain and ventral nerve cord but is not required to maintain neuroblast numbers or for the regulation of temporal series factor expression in neuroblasts. However, loss of Unk increases the number of neuroblasts and GMCs in S-phase of the cell cycle, resulting in the overproduction of neurons. We also show that Unk interacts with Hdc through its zinc finger domain. The zinc finger domain is required for the synergistic activity of Unk with Hdc during eye development but is not necessary for the activity of Unk in thoracic neurogenesis. Overall, this study shows that Unk and Hdc are novel negative regulators of neurogenesis in Drosophila and indicates a conserved role of mTOR signalling in nervous system development.

中文翻译：

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mTOR 通路成分 Unkempt 调节果蝇中枢神经系统中的神经干细胞和神经祖细胞周期。


复杂神经系统的形成需要祖细胞增殖、分化和成熟的协调作用。果蝇胚胎后中枢神经系统为剖析支持神经发生的细胞和分子机制提供了一个强大的模型。我们之前发现保守的锌指/环蛋白 Unkempt (Unk) 是果蝇眼睛发育过程中神经元分化的关键时间调节因子，并表明 Unk 与其结合伙伴 Headcase 一起在雷帕霉素 (mTOR) 途径的机械靶标下游发挥作用。高清）。在这里，我们研究 Unk 在果蝇胚胎后胸神经发生中的作用。果蝇中枢神经系统包含神经干细胞（称为神经母细胞）和神经祖细胞（称为神经节母细胞（GMC））。 Unk 在中枢脑和腹神经索中高度表达，但不需要维持神经母细胞数量或调节神经母细胞中的时间序列因子表达。然而，Unk 的缺失会增加细胞周期 S 期神经母细胞和 GMC 的数量，导致神经元的过度产生。我们还表明 Unk 通过其锌指结构域与 Hdc 相互作用。锌指结构域对于眼睛发育过程中 Unk 与 Hdc 的协同活性是必需的，但对于胸神经发生中 Unk 的活性不是必需的。总的来说，这项研究表明 Unk 和 Hdc 是果蝇神经发生的新型负调节因子，并表明 mTOR 信号在神经系统发育中的保守作用。