Formation of the Drosophila salivary gland

果蝇唾液腺的形成

• 批准号: 7145417
• 负责人: Deborah J Andrew
• 金额: $ 37.32万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-02-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7145417
• 关键词: Drosophilidae; arthropod genetics; biological signal transduction; cell migration; developmental genetics; embryo /fetus tissue /cell culture; gene expression; gene mutation; gene targeting; genetic regulation; histogenesis; molecular cloning; mutant; protein protein interaction; protein structure function; salivary glands; transcription factor

DESCRIPTION (provided by applicant): During development, organ precursors are specified through a combination of localized transcription factors and signaling events. Cell growth, rearrangement and directed migration shape and position organs as they develop. Ultimately, cells within different organs acquire unique physiological adaptations that allow them to perform their specialized functions. Many of the molecular pathways that function during the development of specific organs are also required to maintain function in the adult structures. Failure to achieve and maintain specialized functions often leads to organ failure and degeneration, and is thus linked to several human diseases and birth defects. To learn how organs form and acquire their unique physiological adaptations, we are using a simple model: the Drosophila salivary gland, which is the largest secretory organ in the animal. It is comprised of two paired secretory tubes, which synthesize and secrete large amounts of proteins, and smaller duct tubes, which connect the secretory tubes to the mouth and serve as a conduit for the salivary gland secretions. In previous work, we and others have identified the localized transcription factors and signaling pathways that determine where the salivary gland will form, that control the number of cells recruited to a salivary gland fate and that distinguish among the major cell types in this organ. We have also identified six early expressed transcription factors that have profound effects on salivary gland morphology and physiology. In this application, we propose to (1) identify the downstream targets of the six transcription factor genes that are expressed in the early salivary gland and are key to gland morphogenesis and physiology; (2) to determine the relative contributions of cell shape change and cell rearrangement to tube formation; and (3) determine how surrounding tissues contribute to the final correct placement of the salivary gland. In aim 1, we will use whole mount in situ hybridization to determine which of 193+ known salivary gland genes are regulated by each of the six transcription factor genes. In aim 2, we will use live imaging of marked cells to determine how much cell rearrangement normally occurs during tube invagination and elongation, and we will characterize a key subset of the transcriptional targets of the genes that mediate cell shape change and rearrangement. In aim 3, we will characterize signaling pathways necessary for the salivary gland to navigate to its correct final position.

描述（由申请人提供）：在开发过程中，通过局部转录因子和信号事件的结合来指定器官前体。随着它们的发展，细胞生长，重排和定向迁移形状和位置器官。最终，不同器官中的细胞获得了独特的生理适应，使其能够执行其专业功能。在特定器官发展过程中功能的许多分子途径也需要保持成人结构中的功能。未能实现和维护专业功能通常会导致器官衰竭和变性，因此与几种人类疾病和先天缺陷有关。为了了解器官如何形成和获取其独特的生理适应，我们使用了一个简单的模型：果蝇唾液腺，果蝇是动物中最大的分泌器官。它由两个配对的分泌管组成，它们合成和分泌大量的蛋白质和较小的管道管，它们将分泌管连接到口腔，并用作唾液腺分泌物的管道。在先前的工作中，我们和其他人已经确定了决定唾液腺将在哪里形成的局部转录因子和信号传导途径，这些途径控制着募集到唾液腺命运的细胞数量，并区分该器官中主要细胞类型的细胞。我们还确定了六个早期表达的转录因子，这些因子对唾液腺形态和生理学具有深远影响。在此应用中，我们建议（1）确定在早期唾液腺中表达的六个转录因子基因的下游靶标，并且是腺形态发生和生理学的关键； （2）确定细胞形状变化和细胞重排对管形成的相对贡献； （3）确定周围组织如何促进唾液腺的最终正确放置。在AIM 1中，我们将使用整个原位杂交来确定六个转录因子基因中的每一个都调节了193+已知的唾液腺基因中的哪一个。在AIM 2中，我们将使用标记细胞的实时成像来确定在管道内陷和伸长期间通常发生多少细胞重排，并且我们将表征介导细胞形状变化和重排的基因转录靶标的关键子集。在AIM 3中，我们将表征唾液腺导航到其正确的最终位置所需的信号通路。