split ends, a new component of the Drosophila EGF receptor pathway, regulates development of midline glial cells
split ends, a new component of the Drosophila EGF receptor pathway, regulates development of midline glial cells
复制标题
DOI：
10.1016/s0960-9822(00)00625-4
复制
发表时间：
2000-07-27
期刊：
影响因子：
9.2
通讯作者：
Rebay, I
中科院分区：
文献类型：
--
作者：
Chen, FL;Rebay, I
DER（果蝇表皮生长因子受体酪氨酸激酶 (RTK)）的信号传导对于胚胎中枢神经系统 (CNS) 中线神经胶质细胞 (MGC) 的正常迁移和存活至关重要 [1-4]。我们最近在旨在识别 RTK/Ras 途径新成分的筛选中分离出了一种名为分叉末端 (spen) 的基因 [5]，果蝇 Spen 及其直向同源物的特征是一组独特的 RNA 识别基序 (RRM) 和 SPOC 结构域，这是一种功能未知的高度保守的羧基末端结构域 [5-7]。为了研究 RTK 信号传导背景下的 spen 功能，我们研究了 spen 功能丧失突变对胚胎中枢神经系统发育的影响。我们发现，spen 是 MGC 正常迁移和存活所必需的，并且缺乏 spen 的胚胎具有 CNS 缺陷，这与 DER 信号通路的几个已知组件的突变体中所见的缺陷惊人地相似。此外，spen 与所指出的 RTK 效应器具有协同相互作用。使用 MGC 靶向表达，我们发现增加的 Ras 信号传导挽救了与显性负性 spen 转基因表达相关的致死性，因此，spen 编码 DER/Ras 信号传导途径的正作用成分。 (C) 2000 Elsevier Science Ltd. 保留所有权利。
Signaling by DER, the Drosophila epidermal growth factor receptor tyrosine kinase (RTK), is essential for proper migration and survival of midline glial cells (MGCs) in the embryonic central nervous system (CNS) [1-4]. We recently isolated a gene called split ends (spen) in a screen designed to identify new components of the RTK/Ras pathway [5], Drosophila Spen and its orthologs are characterized by a distinct set of RNA recognition motifs (RRMs) and a SPOC domain, a highly conserved carboxy-terminal domain of unknown function [5-7]. To investigate spen function in the context of RTK signaling, we examined the consequences of spen loss-of-function mutations on embryonic CNS development. We found that spen was required for normal migration and survival of MGCs and that embryos lacking spen had CNS defects strikingly reminiscent of those seen in mutants of several known components of the DER signaling pathway. In addition, spen interacted synergistically with the RTK effector pointed. Using MGC-targeted expression, we found that increased Ras signaling rescued the lethality associated with expression of a dominant negative spen transgene, Therefore, spen encodes a positively acting component of the DER/Ras signaling pathway. (C) 2000 Elsevier Science Ltd. Ail rights reserved.