Translational readthrough in the hdc mRNA generates a novel branching inhibitor in the Drosophila trachea
Translational readthrough in the hdc mRNA generates a novel branching inhibitor in the Drosophila trachea
复制标题
DOI：
10.1101/gad.12.7.956
复制
发表时间：
1998-04-01
影响因子：
10.5
通讯作者：
Samakovlis, C
中科院分区：
文献类型：
--
作者：
Steneberg, P;Englund, C;Samakovlis, C
在许多分支管状器官（包括果蝇气管）的发育中，一个核心问题是控制从先前存在的血管产生的新分支的数量和模式的机制和分子。我们报告了一种分支抑制剂，Fusion-6（Fus-6），由专门的气管细胞产生，以防止相邻细胞分支。在Fus-6突变体中，通常静止的细胞获得分支命运，并形成从初级分支发出的芽的数量增加。Fus-6被鉴定为headcase（hdc）基因，并在延伸融合芽以互连气管网络的细胞亚群中表达。HDC表达受转录因子蜗牛（ESG）调节，因为它在ESG突变体的融合细胞中不表达，并且在气管中响应ESG错误表达而异位激活。我们发现，hdc mRNA编码两个重叠的蛋白质产物的翻译终止机制的不寻常的抑制。翻译通读对于hdc功能是必要的，因为气管突变表型的拯救需要全长hdc mRNA。在异位表达实验与全长和截短的hdc结构，只有全长cDNA编码的蛋白质可以抑制末端分支。我们认为hdc在抑制性信号机制中非自主地起作用，以决定在气管中形成单细胞芽的细胞数量。
A central question in the development of many branched tubular organs, including the Drosophila trachea, concerns the mechanisms and molecules that control the number and pattern of new branches arising from preexisting vessels. We report on a branching inhibitor, Fusion-6 (Fus-6) produced by specialized tracheal cells to prevent neighboring cells from branching. In Fus-6 mutants, cells that are normally quiescent acquire the branching fate and form an increased number of sprouts emanating from the primary branches. Fus-6 is identified as the headcase (hdc) gene and is expressed in a subset of the cells that extend fusion sprouts to interconnect the tracheal network. hdc expression is regulated by the transcription factor escargot (esg) because it is not expressed in the fusion cells of esg mutants and is ectopically activated in the trachea in response to esg misexpression. We show that the hdc mRNA encodes two overlapping protein products by an unusual suppression of translational termination mechanism. Translational readthrough is necessary for hdc function because rescue of the tracheal mutant phenotype requires the full-length hdc mRNA. In ectopic expression experiments with full-length and truncated hdc constructs, only the full-length cDNA encoding both proteins could inhibit terminal branching. We propose that hdc acts non-autonomously in an inhibitory signaling mechanism to determine the number of cells that will form unicellular sprouts in the trachea.