Dilp-2-mediated PI3-kinase activation coordinates reactivation of quiescent neuroblasts with growth of their glial stem cell niche
Dilp-2-mediated PI3-kinase activation coordinates reactivation of quiescent neuroblasts with growth of their glial stem cell niche
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DOI：
10.1371/journal.pbio.3000721
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发表时间：
2020-05-01
期刊：
影响因子：
9.8
通讯作者：
Siegrist, Sarah E.
中科院分区：
文献类型：
--
作者：
Yuan, Xin;Sipe, Conor W.;Siegrist, Sarah E.
膳食营养素提供生物体生长和发育所必需的大分子。为了响应动物进食，进化上保守的生长信号传导途径被激活，导致细胞增殖和组织生长的速率增加。目前尚不清楚发育中的组织内不同类型的细胞如何协调生长以响应膳食营养素，以及不同细胞类型的协调生长是否是正常组织功能所必需的。在这里，我们报告说，果蝇神经干细胞，被称为神经母细胞，重新激活从发展静止在饮食营养依赖的方式。脑中的神经母细胞再活化需要来自皮质胶质细胞和气管过程的磷酸肌醇3-激酶（PI 3-激酶）信号的非自主活化，这两者都与神经母细胞密切相关。此外，神经母细胞中的PI 3-激酶激活是神经胶质膜扩张和神经母细胞-神经胶质细胞接触所必需的。最后，PI 3-激酶是神经母细胞、神经胶质细胞和气管的营养依赖性生长所需的细胞自主性。在7种果蝇胰岛素样肽（Dilps）中，我们发现Dilp-2是PI 3激酶激活以及大脑中成神经细胞和胶质细胞之间生长协调所需的。Dilp-2诱导大脑皮层胶质细胞启动膜生长，并与静止的神经母细胞进行首次接触。接触后，神经母细胞的大小增加，并重新进入S期。一旦从静止状态重新激活，神经母细胞促进皮质胶质细胞的生长，皮质胶质细胞反过来在神经母细胞及其新生后代周围形成选择性膜屏障。我们的研究结果强调了神经干细胞和周围细胞类型之间双向生长信号对营养的重要性，并展示了不同细胞类型之间的协调生长如何驱动组织形态发生和功能。
Dietary nutrients provide macromolecules necessary for organism growth and development. In response to animal feeding, evolutionarily conserved growth signaling pathways are activated, leading to increased rates of cell proliferation and tissue growth. It remains unclear how different cell types within developing tissues coordinate growth in response to dietary nutrients and whether coordinated growth of different cell types is necessary for proper tissue function. Here, we report that Drosophila neural stem cells, known as neuroblasts, reactivate from developmental quiescence in a dietary-nutrient-dependent manner. Neuroblast reactivation in the brain requires nonautonomous activation of phosphoinositide 3-kinase (PI3-kinase) signaling from cortex glia and tracheal processes, both of which are closely associated with neuroblasts. Furthermore, PI3-kinase activation in neuroblasts is required nonautonomously for glial membrane expansion and robust neuroblast-glial contact. Finally, PI3-kinase is required cell autonomously for nutrient-dependent growth of neuroblasts, glia, and trachea. Of the 7 Drosophila insulin-like peptides (Dilps), we find that Dilp-2 is required for PI3-kinase activation and growth coordination between neuroblasts and glia in the brain. Dilp-2 induces brain cortex glia to initiate membrane growth and make first contact with quiescent neuroblasts. After contact, neuroblasts increase in size and reenter S-phase. Once reactivated from quiescence, neuroblasts promote growth of cortex glia, which, in turn, form a selective membrane barrier around neuroblasts and their newborn progeny. Our results highlight the importance of bidirectional growth signaling between neural stem cells and surrounding cell types in the brain in response to nutrition and demonstrate how coordinated growth among different cell types drives tissue morphogenesis and function.