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Dilp-2-mediated PI3-kinase activation coordinates reactivation of quiescent neuroblasts with growth of their glial stem cell niche.
PLOS Biology ( IF 7.8 ) Pub Date : 2020-05-28 , DOI: 10.1371/journal.pbio.3000721
Xin Yuan 1 , Conor W Sipe 1, 2 , Miyuki Suzawa 3 , Michelle L Bland 3 , Sarah E Siegrist 1
Affiliation  

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.



中文翻译:

Dilp-2 介导的 PI3 激酶激活协调静止神经母细胞的重新激活与其神经胶质干细胞生态位的生长。

膳食营养素提供生物体生长和发育所必需的大分子。作为对动物喂养的反应,进化上保守的生长信号通路被激活,导致细胞增殖和组织生长的速度增加。目前尚不清楚发育组织内的不同细胞类型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对正常组织功能是必要的。在这里,我们报告果蝇神经干细胞,称为神经母细胞,以依赖饮食营养的方式从发育静止状态重新激活。大脑中的神经母细胞重新激活需要来自皮质神经胶质和气管过程的磷酸肌醇 3-激酶 (PI3-激酶) 信号的非自主激活,这两者都与神经母细胞密切相关。此外,神经母细胞中的 PI3-激酶激活是神经胶质膜扩张和神经母细胞 - 神经胶质接触的非自主性所必需的。最后,神经母细胞、神经胶质和气管的营养依赖性生长需要细胞自主地使用 PI3-激酶。7果蝇胰岛素样肽 (Dilps),我们发现 Dilp-2 是 PI3 激酶激活和大脑中神经母细胞和神经胶质之间的生长协调所必需的。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首次接触。接触后,神经母细胞体积增加并重新进入 S 期。一旦从静止状态重新激活,神经母细胞就会促进皮层神经胶质的生长,进而在神经母细胞及其新生后代周围形成选择性膜屏障。我们的结果强调了大脑中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,并证明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。

更新日期:2020-05-28
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