Oocyte development in Drosophila

项目描述（申请人提供）：本项目的长期目标是以果蝇卵发生为模型系统阐明配子发育机制，为果蝇遗传和细胞生物学研究提供有力的工具。一个重要的健康问题是，成年人生殖系细胞暴露于诸如营养不良和接触攻击性药物等环境压力下的存活。在这个项目中进行的研究将影响对未成熟配子在恶劣条件下确保其生存的保护机制的理解。该项目还将研究配子发育的一个基本和保守的方面——部分或全部动物配子发生在合胞细胞群中，这些细胞群通过称为环管的细胞间桥连接。通过生殖系环管调节细胞质胞间运动以响应营养有效性的机制将被检查。体细胞卵泡细胞之间也存在环管

DESCRIPTION (provided by applicant): The long-term goal of this project is to elucidate mechanisms of gamete development using Drosophila oogenesis as a model system, and the powerful tools available for genetic and cell biological approaches in Drosophila. A significant health concern is the survival of germline cells in adults exposed to environmental stresses such as poor nutrition and exposure to aggressive pharmaceuticals. Research carried out in this project will impact understanding of protective mechanisms used by immature gametes to ensure their survival through harsh conditions. This project will also investigate a fundamental and conserved aspect of gamete development - some or all of animal gametogenesis occurs in syncytial clusters of cells connected by intercellular bridges called ring canals. Mechanisms modulating intercellular movement of cytoplasm through germline ring canals in response to nutrient availability will be examined. Ring canals are also present between somatic follicle cells of the Drosophila egg chamber, although their function is not known. This project will investigate movement of cytoplasmic components through somatic ring canals, and use novel approaches for disrupting somatic ring canals to determine their function. This information will impact understanding of intercellular movement through small ring canals similar to those connecting developing spermatocytes. In addition, tools developed in this research will be useful for examining somatic ring canals in other Drosophila tissues. Aim 1 will use genetic approaches to determine the mechanism of the starvation response in oocyte development, by manipulating components of the Drosophila Insulin/insulin-like (IIS)/Tor pathway. Previtellogenic egg chambers mount a response to poor nutrition that includes enlarged P bodies and reorganization of the microtubules. Multiple components of the IIS/Tor pathway will be expressed or knocked down, individually or in combinations, in either the germline or the follicle cell tissues to characterize the consequences in starved egg chambers. New approaches will allow tracking of egg chambers that have been starved to examine their recovery in detail, and mutants affecting P body assembly will be used determine the consequences of crippling the starvation response. Aim 2 will use new cell marking techniques and fluorescent proteins to illuminate the function of ring canals in the follicle cell epithelium that surrounds the egg chamber. Experiments will determine whether ring canals serve to equilibrate protein levels between transcriptionally uncoordinated cells. New methods for targeted disruption of somatic ring canals will allow phenotypic analysis of disrupted syncytia, which have been elusive. The importance of the role that follicle cell syncytia play during egg chamber development will be better defined following these studies, and these new methods can then be applied to other somatic syncytia involved in development in Drosophila.