Programmed Cell Death in Drosophila Development

果蝇发育中的程序性细胞死亡

• 批准号: 6930516
• 负责人: Kimberly A McCall
• 金额: $ 35.29万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2008-03-09
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6930516
• 关键词: Drosophilidae; apoptosis; arthropod genetics; biological signal transduction; cell growth regulation; cysteine endopeptidases; egg /ovum; enzyme induction /repression; enzyme inhibitors; gene expression; gene mutation; gene targeting; genetic mapping; genetic regulation; genetically modified animals; growth /development; histology; in situ hybridization; invertebrate embryology; lamins; molecular cloning; morphometry; oogenesis; protein localization; protein structure function; western blottings

DESCRIPTION (provided by applicant): Programmed cell death plays a central role in development and in multiple diseases, notably cancer and neurodegenerative disorders. -The long-term objective of this proposed research is to further understand the mechanisms of programmed cell death and its role in development. The model being used is the ovary of the fruitfly, Drosophila melanogaster, a system with unique advantages for the study of cell death. Programmed cell death of ovarian nurse cells is essential for proper oocyte development. Nurse cells possess distinct traits which make them an ideal model for analyzing cell death in vivo. These cells are abundant, die synchronously in clusters, and are large, making them amenable to subcellular analyses. Furthermore, disruption of nurse cell death results in sterility, a phenotype that permits straightforward genetic analysis. This proposal addresses multiple aspects of the nurse cell death pathway. The specific aims are to 1) further address the requirement for caspases in this pathway by the expression of constitutively active Drosophila caspase- 1 (Dcp- 1) in the germline, the characterization of new alleles of dcp-1, and the characterization of the caspase Drice; 2) isolate additional genes involved in nurse cell death by histological examination of mutants previously shown to have defects in oogenesis; and 3) test the role of individual caspase targets during cell death in vivo by the expression of cleavage-defective molecules. These experiments should yield an understanding of the molecules that are critical for nurse cell death, from the initial signal to the final proteolyzed targets. This knowledge is likely to have implications for other cell death pathways in Drosophila and other organisms.

描述（由申请人提供）：程序性细胞死亡起着核心作用 发育和多种疾病，特别是癌症和神经退行性疾病 失调。 -这项研究的长期目标是进一步 了解程序性细胞死亡的机制及其在发育中的作用。 所使用的模型是果蝇（Drosophila melanogaster）的卵巢， 系统对于细胞死亡的研究具有独特的优势。程序化细胞 卵巢护理细胞的死亡对于卵母细胞的正常发育至关重要。护士 细胞具有独特的特征，这使其成为分析细胞的理想模型 体内死亡。这些细胞数量丰富，成簇同步死亡，并且 大，使它们适合亚细胞分析。此外，破坏 护士细胞死亡导致不育，这是一种允许简单直接的表型 遗传分析。该提案涉及护士小组的多个方面 死亡途径。具体目标是 1) 进一步满足以下要求： 通过组成型活性果蝇的表达来控制该途径中的半胱天冬酶 种系中的 caspase- 1 (Dcp- 1)，新等位基因的表征 dcp-1，以及 caspase Drice 的表征； 2）隔离额外的 通过突变体的组织学检查发现参与护士细胞死亡的基因 先前显示卵子发生有缺陷； 3）测试角色 体内细胞死亡过程中个体 caspase 的靶标是 裂解缺陷分子。这些实验应该能产生理解 对护士细胞死亡至关重要的分子，从最初 向最终蛋白水解目标发出信号。这些知识很可能有 对果蝇和其他生物体中其他细胞死亡途径的影响。