The Drosophila dysfusion basic helix-loop-helix (bHLH)-PAS gene controls tracheal fusion and levels of the trachealess bHLH-PAS protein

The Drosophila dysfusion basic helix-loop-helix (bHLH)-PAS gene controls tracheal fusion and levels of the trachealess bHLH-PAS protein
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DOI:
10.1128/mcb.23.16.5625-5637.2003
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发表时间:
2003-08-01
影响因子:
5.3
通讯作者:
Crews, ST
Crews, ST
中科院分区:
生物学2区
文献类型:
--
作者:
Jiang, L;Crews, ST

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成熟昆虫气管的发育需要一系列复杂的细胞事件,包括气管细胞规格、细胞迁移、小管分支和小管融合。在这里,我们描述了果蝇黑腹融合不良基因的鉴定,该基因编码一种新的碱性螺旋-环-螺旋(BHLH)-PAS蛋白,在秀丽线虫、昆虫和人类之间保守,并控制气管融合事件。差异融合蛋白在体内作为异源二聚体与Tango bHLH-PAS蛋白形成推测的DNA结合复合体。融合不良基因在多种类型的胚胎细胞中表达,包括气管融合细胞、前缘细胞、前庭细胞、神经系统细胞、后肠细胞和肛垫细胞。RNAi实验表明,背支、侧干和神经节支融合需要失血,而背干融合不需要。蜗牛基因也在融合细胞中表达,是气管融合所必需的,它先于融合表达。对蜗牛突变体的分析表明了一种复杂的失血调节模式,即失血表达依赖于蜗牛在背侧和神经节分支中的表达,而不是背干。在气管发育的早期,所有气管细胞中的TracHealth less bHLH-PAS蛋白水平都很高,但由于野生型融合细胞中融合不良的水平上升,融合细胞中的TracHealth水平下降。TracHealess的下调依赖于血液灌流功能障碍。这些结果表明,基本螺旋-环-螺旋-PAS蛋白(差异融合蛋白、TracHealth蛋白,可能还有类似蛋白)之间的竞争性相互作用可能对气管的正常发育很重要。
The development of the mature insect trachea requires a complex series of cellular events, including tracheal cell specification, cell migration, tubule branching, and tubule fusion. Here we describe the identification of the Drosophila melanogaster dysfusion gene, which encodes a novel basic helix-loop-helix (bHLH)-PAS protein conserved between Caenorhabditis elegans, insects, and humans, and controls tracheal fusion events. The Dysfusion protein functions as a heterodimer with the Tango bHLH-PAS protein in vivo to form a putative DNA-binding complex. The dysfusion gene is expressed in a variety of embryonic cell types, including tracheal-fusion, leading-edge, foregut atrium cells, nervous system, hindgut, and anal pad cells. RNAi experiments indicate that dysfusion is required for dorsal branch, lateral trunk, and ganglionic branch fusion but not for fusion of the dorsal trunk. The escargot gene, which is also expressed in fusion cells and is required for tracheal fusion, precedes dysfusion expression. Analysis of escargot mutants indicates a complex pattern of dysfusion regulation, such that dysfusion expression is dependent on escargot in the dorsal and ganglionic branches but not the dorsal trunk. Early in tracheal development, the Trachealess bHLH-PAS protein is present at uniformly high levels in all tracheal cells, but since the levels of Dysfusion rise in wild-type fusion cells, the levels of Trachealess in fusion cells decline. The downregulation of Trachealess is dependent on dysfusion function. These results suggest the possibility that competitive interactions between basic helix-loop-helix-PAS proteins (Dysfusion, Trachealess, and possibly Similar) may be important for the proper development of the trachea.