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）：在发育过程中，器官前体是通过局部转录因子和信号事件的组合来指定的。细胞生长、重排和定向迁移决定器官发育时的形状和位置。最终，不同器官内的细胞获得独特的生理适应，使它们能够执行其专门的功能。在特定器官发育过程中发挥作用的许多分子途径也需要维持成人结构的功能。无法实现和维持专门的功能通常会导致器官衰竭和退化，从而与多种人类疾病和出生缺陷有关。为了了解器官如何形成并获得其独特的生理适应，我们使用一个简单的模型：果蝇唾液腺，它是动物中最大的分泌器官。它由两对合成和分泌大量蛋白质的分泌管和将分泌管连接到口腔并充当唾液腺分泌物的导管的较小导管组成。在之前的工作中，我们和其他人已经确定了局部转录因子和信号通路，它们决定了唾液腺的形成位置，控制着唾液腺命运所招募的细胞数量，并区分了该器官中的主要细胞类型。我们还鉴定了六种早期表达的转录因子，它们对唾液腺形态和生理学具有深远的影响。在此应用中，我们建议（1）确定在早期唾液腺中表达且对腺体形态发生和生理学至关重要的六个转录因子基因的下游靶标； (2)确定细胞形状变化和细胞重排对管形成的相对贡献； (3) 确定周围组织如何有助于唾液腺的最终正确放置。在目标 1 中，我们将使用整体原位杂交来确定 193 多个已知唾液腺基因中的哪些基因受到 6 个转录因子基因中的每一个的调节。在目标 2 中，我们将使用标记细胞的实时成像来确定在管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。在目标 3 中，我们将描述唾液腺导航至正确的最终位置所需的信号通路。