SD and VG proteins in drosophila development

果蝇发育中的 SD 和 VG 蛋白

• 批准号: 9704-2008
• 负责人: Bell, John
• 金额: $ 3.64万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2008
• 资助国家: 加拿大
• 起止时间: 2008-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=390008
• 关键词: SD; VG; proteins; drosophila; development

My research program aims at increasing our understanding of the functional interactions among genes that direct the development of complex organs in a eukaryote. The model system used is Drosophila and the approach is to do a genetic and molecular biological analysis of some of the specific genes involved in wing formation and how some of the same genes have broader roles in organogenesis in non-wing tissues. Past work in the laboratory concentrated on analysis of the role of the vestigial (vg) gene in wing development and how vg interacts functionally with the scalloped (sd) gene. The sd gene is vital, in that homozygous mutations may be lethal. It is known that sd is a member of a highly conserved family of transcriptions factors (the TEA/ATTS domain proteins) and, as such, has a fundamental role in Drosophila development whereas vg seems to be required only in the wing. A fusion gene has been produced which includes full length vg and the sdTEA domain (about 30% of SD) and when this protein is expressed it can rescue sd or vg mutations, and even sd, vg double mutations. Thus, the encoded protein behaves like the natural VG/SD complex in the context of wing development. Further, 70% of the SD protein is not required for wing formation even though SD is a vital protein. A significant aspect of this work is that the human TEF-1 gene is a homologue of sd and can actually rescue sd mutations when transformed into flies. Particular effort is now directed towards the function of sd in non-wing tissues. We have discovered protein binding partners for SD in muscle and nervous tissue and feel that the vital function of SD is involved in the development of these tissues. In fact, sd null mutant flies, which are lethal as homozygotes, do not develop a normal heart. We are also characterizing post-translational modifications that occur on the VG and SD proteins in attempts to elucidate how and when these proteins bind to each other, and in the case of SD to proteins in other tissues as well. The genes involved in Drosophila muscle development have vertebrate homologues. Hence, data gathered in this model system have a significant likelihood of helping us to understand the more complex vertebrate systems.

我的研究项目旨在增加我们对基因之间功能相互作用的理解，这些基因指导真核生物复杂器官的发育。 使用的模型系统是果蝇，方法是对参与翅膀形成的一些特定基因进行遗传和分子生物学分析，以及一些相同的基因如何在非翅膀组织的器官发生中发挥更广泛的作用。过去的实验室工作集中在分析退化基因（vg）在翅膀发育中的作用，以及vg与扇贝基因（sd）在功能上的相互作用。 sd基因是至关重要的，因为纯合突变可能是致命的。 众所周知，sd是一个高度保守家族的translucent因子（TEA/ATTS结构域蛋白）的成员，因此，在果蝇发育中具有重要作用，而vg似乎只在翅膀中需要。 已经产生了融合基因，其包括全长vg和sdTEA结构域（约SD的30%），并且当表达该蛋白质时，其可以拯救sd或vg突变，甚至sd、vg双突变。 因此，编码的蛋白质在翅膀发育的背景下表现得像天然的VG/SD复合物。此外，70%的SD蛋白质不是翅膀形成所需的，即使SD是一种重要的蛋白质。这项工作的一个重要方面是，人类TEF-1基因是sd的同源物，当转化到果蝇中时，实际上可以挽救sd突变。 现在特别的努力是针对sd在非翅膀组织中的功能。我们已经在肌肉和神经组织中发现了SD的蛋白质结合伴侣，并认为SD的重要功能与这些组织的发育有关。 事实上，sd零突变果蝇，作为纯合子是致命的，不会发育出正常的心脏。我们还表征了VG和SD蛋白上发生的翻译后修饰，试图阐明这些蛋白质如何以及何时相互结合，以及在SD的情况下与其他组织中的蛋白质结合。 与果蝇肌肉发育有关的基因与脊椎动物有同源性。因此，在这个模型系统中收集的数据有很大的可能帮助我们理解更复杂的脊椎动物系统。