Control of Drosophila perineurial glial growth by interacting neurotransmitter-mediated signaling pathways.
Control of Drosophila perineurial glial growth by interacting neurotransmitter-mediated signaling pathways.
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通过相互作用的神经递质介导的信号通路控制果蝇神经周围胶质细胞的生长。
DOI：
10.1073/pnas.191107698
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发表时间：
2001
影响因子：
11.1
通讯作者：
Stern,M
中科院分区：
文献类型：
--
作者：
Yager,J;Richards,S;Hekmat-Scafe,DS;Hurd,DD;Sundaresan,V;Caprette,DR;Saxton,WM;Carlson,JR;Stern,M
果蝇外周神经在结构上类似于哺乳动物的外周神经，包括轴突和内部神经胶质层，由外部神经束膜神经胶质层包围。尽管已经确定外周神经内的细胞之间发生细胞间通讯，但所使用的信号传导途径以及这种信号传导对神经结构和功能的影响仍然不完全清楚。在这里，我们用遗传学方法证明果蝇外周神经是研究细胞间信号传导的有利系统。我们发现，神经束膜神经胶质细胞的生长是由5个基因之间的相互作用控制的：ine，它编码一种假定的神经递质转运蛋白;eag，它编码一种钾通道;push，它编码一种大的含锌指蛋白;amn，它编码一种假定的与垂体腺苷酸环化酶激活肽相关的神经肽;和NF 1，果蝇中负责1型神经纤维瘤病的人类基因的直系同源物。在其他果蝇系统中，pusandNF 1是由Amn或垂体腺苷酸环化酶激活肽介导的信号通路所必需的。我们的研究结果支持一种模型，其中Amn神经肽，通过推和NF 1，抑制神经束膜胶质细胞的生长，而Ine的底物神经递质促进神经束膜胶质细胞的生长。周围神经内细胞间信号传导的缺陷可能是神经纤维瘤形成的基础，神经纤维瘤病的标志。
Drosophilaperipheral nerves, similar structurally to the peripheral nerves of mammals, comprise a layer of axons and inner glia, surrounded by an outer perineurial glial layer. Although it is well established that intercellular communication occurs among cells within peripheral nerves, the signaling pathways used and the effects of this signaling on nerve structure and function remain incompletely understood. Here we demonstrate with genetic methods that theDrosophilaperipheral nerve is a favorable system for the study of intercellular signaling. We show that growth of the perineurial glia is controlled by interactions among five genes:ine, which encodes a putative neurotransmitter transporter;eag, which encodes a potassium channel;push, which encodes a large, Zn2+-finger-containing protein;amn, which encodes a putative neuropeptide related to the pituitary adenylate cyclase activator peptide; andNF1, theDrosophilaortholog of the human gene responsible for type 1 neurofibromatosis. In otherDrosophilasystems,pushandNF1are required for signaling pathways mediated by Amn or the pituitary adenylate cyclase activator peptide. Our results support a model in which the Amn neuropeptide, acting through Push and NF1, inhibits perineurial glial growth, whereas the substrate neurotransmitter of Ine promotes perineurial glial growth. Defective intercellular signaling within peripheral nerves might underlie the formation of neurofibromas, the hallmark of neurofibromatosis.