The secreted neurotrophin Spätzle 3 promotes glial morphogenesis and supports neuronal survival and function.
The secreted neurotrophin Spätzle 3 promotes glial morphogenesis and supports neuronal survival and function.
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DOI：
10.1101/gad.305888.117
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发表时间：
2017-10-15
影响因子：
10.5
通讯作者：
Freeman MR
中科院分区：
文献类型：
--
作者：
Coutinho-Budd JC;Sheehan AE;Freeman MR
Coutinho-Budd等人表明，皮质神经胶质细胞彼此平铺并与星形胶质细胞平铺，以建立主动限制神经胶质细胞生长的独特CNS空间域。分泌的神经营养因子Spätzle 3（Spz 3）的缺失导致神经元细胞体的胶质鞘的缺失，增加神经元细胞死亡和动物行为的缺陷。大多数神经胶质功能依赖于与神经元建立密切的形态学关系。在理解神经元-胶质细胞在突触和轴突接触处的信号传导方面已经取得了重大进展，但是胶质细胞如何支持神经元细胞体尚不清楚。在这里，我们探讨了果蝇皮层神经胶质细胞（几乎只与神经元细胞体）的生长和功能，以了解胶质细胞体的相互作用。我们发现，皮质胶质细胞瓷砖彼此和星形胶质细胞建立独特的中枢神经系统（CNS）的空间域，积极限制胶质细胞的生长，和皮质胶质细胞的选择性消融导致动物死亡。在基于RNAi的筛选中，我们确定了αSNAP（可溶性NSF [N-乙基马来酸敏感因子]附着蛋白α）和囊泡融合和再循环机制的几种组分对于维持皮质胶质细胞形态和与神经元的持续接触至关重要。有趣的是，分泌的神经营养因子Spätzle 3（Spz 3）的缺失表现为αSNAP表型，包括神经元细胞体的神经胶质鞘的缺失，神经元细胞死亡的增加和动物行为的缺陷。救援实验表明，Spz 3只能在很短的距离内发挥这些作用。这项工作确定了神经元细胞体在CNS稳态中的神经胶质鞘化的重要作用，以及Spz 3作为维持皮质神经胶质形态和神经元-神经胶质接触所需的新型信号传导因子。
Coutinho-Budd et al. show that cortex glia tile with one another and with astrocytes to establish unique CNS spatial domains that actively restrict glial growth. Loss of the secreted neurotrophin Spätzle 3 (Spz3) caused the loss of glial ensheathment of neuron cell bodies, increased neuronal cell death, and defects in animal behavior. Most glial functions depend on establishing intimate morphological relationships with neurons. Significant progress has been made in understanding neuron–glia signaling at synaptic and axonal contacts, but how glia support neuronal cell bodies is unclear. Here we explored the growth and functions of Drosophila cortex glia (which associate almost exclusively with neuronal cell bodies) to understand glia–soma interactions. We show that cortex glia tile with one another and with astrocytes to establish unique central nervous system (CNS) spatial domains that actively restrict glial growth, and selective ablation of cortex glia causes animal lethality. In an RNAi-based screen, we identified αSNAP (soluble NSF [N-ethylmalemeide-sensitive factor] attachment protein α) and several components of vesicle fusion and recycling machinery as essential for the maintenance of cortex glial morphology and continued contact with neurons. Interestingly, loss of the secreted neurotrophin Spätzle 3 (Spz3) phenocopied αSNAP phenotypes, which included loss of glial ensheathment of neuron cell bodies, increased neuronal cell death, and defects in animal behavior. Rescue experiments suggest that Spz3 can exert these effects only over very short distances. This work identifies essential roles for glial ensheathment of neuronal cell bodies in CNS homeostasis as well as Spz3 as a novel signaling factor required for maintenance of cortex glial morphology and neuron–glia contact.
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影响因子：
6.2
作者：
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通讯作者：
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