The numerous neurons and glia that form the brain originate from tightly controlled growth and division of neural stem cells, regulated systemically by important known stem cell-extrinsic signals. However, the cell-intrinsic mechanisms that control the distinctive proliferation rates of individual neural stem cells are unknown. Here, we show that the size and division rates of Drosophila neural stem cells (neuroblasts) are controlled by the highly conserved RNA binding protein Imp (IGF2BP), via one of its top binding targets in the brain, myc mRNA. We show that Imp stabilises myc mRNA leading to increased Myc protein levels, larger neuroblasts, and faster division rates. Declining Imp levels throughout development limit myc mRNA stability to restrain neuroblast growth and division, and heterogeneous Imp expression correlates with myc mRNA stability between individual neuroblasts in the brain. We propose that Imp-dependent regulation of myc mRNA stability fine-tunes individual neural stem cell proliferation rates.

中文翻译：

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Imp / IGF2BP水平通过myc mRNA稳定性调节个体神经干细胞的生长和分裂

形成大脑的众多神经元和神经胶质来自严格控制的神经干细胞的生长和分裂，神经干细胞的生长和分裂受到重要的已知干细胞外源信号的系统调节。但是，控制单个神经干细胞独特增殖速率的细胞内在机制尚不清楚。在这里，我们显示果蝇神经干细胞（神经母细胞）的大小和分裂率是由高度保守的RNA结合蛋白Imp（IGF2BP）通过其在大脑中的最高结合靶标myc mRNA控制的。我们显示，Imp稳定myc mRNA，从而导致Myc蛋白水平增加，成神经细胞更大，分裂速度更快。在整个开发过程中Imp级别的下降限制了mycmRNA稳定性可抑制神经母细胞的生长和分裂，异质的Imp表达与大脑中单个神经母细胞之间的myc mRNA稳定性相关。我们建议myc mRNA稳定性的Imp依赖调节微调个别神经干细胞增殖率。