Neuroblast niche position is controlled by Phosphoinositide 3-kinase-dependent DE-Cadherin adhesion
Neuroblast niche position is controlled by Phosphoinositide 3-kinase-dependent DE-Cadherin adhesion
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DOI：
10.1242/dev.136713
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发表时间：
2017-03-01
期刊：
影响因子：
4.6
通讯作者：
Siegrist, Sarah E.
中科院分区：
文献类型：
--
作者：
Doyle, Susan E.;Pahl, Matthew C.;Siegrist, Sarah E.
干细胞在其小生境中的正确定位对于组织形态发生和稳态是必不可少的。干细胞如何获得和维持生态位仍然是未知的。在这里，我们表明，一个子集的脑神经母细胞（NB）在果蝇利用磷脂酰肌醇3-激酶（PI 3-激酶）和DE-钙粘蛋白建立粘合剂接触NB利基定位。当NB中的PI 3-激酶活性和DE-钙粘蛋白水平升高时，NB保持在其天然微环境中。这是通过PI 3激酶依赖性调节DE-钙粘蛋白介导的NB和相邻皮质神经胶质细胞之间以及NB和它们的神经节母细胞子细胞之间的细胞粘附而发生的。当NB中PI 3-激酶活性和/或DE-钙粘蛋白水平降低时，NB失去生态位并重新定位到富含神经分泌神经元的非天然脑区域，包括分泌一些果蝇胰岛素样肽的神经元。将PI 3-激酶活性水平与粘附强度联系起来，可以为癌症干细胞和造血干细胞提供从营养不良微环境循环到营养丰富微环境的手段。
Correct positioning of stem cells within their niche is essential for tissue morphogenesis and homeostasis. How stem cells acquire and maintain niche position remains largely unknown. Here, we show that a subset of brain neuroblasts (NBs) in Drosophila utilize Phosphoinositide 3-kinase (PI3-kinase) and DE-cadherin to build adhesive contact for NB niche positioning. NBs remain within their native microenvironment when levels of PI3-kinase activity and DE-cadherin are elevated in NBs. This occurs through PI3-kinase-dependent regulation of DE-Cadherin-mediated cell adhesion between NBs and neighboring cortex glia, and between NBs and their ganglion mother cell daughters. When levels of PI3-kinase activity and/or DE-Cadherin are reduced in NBs, NBs lose niche position and relocate to a non-native brain region that is rich in neurosecretory neurons, including those that secrete some of the Drosophila insulin-like peptides. Linking levels of PI3-kinase activity to the strength of adhesive attachment could provide cancer stem cells and hematopoietic stem cells with a means to cycle from trophic-poor to trophic-rich microenvironments.