SOMATIC CELLS AND SPERMATOCYTE MAINTENANCE IN DROSOPHILA

果蝇体细胞和精母细胞的维持

• 批准号: 6481456
• 负责人: STEPHEN Francis DINARDO
• 金额: $ 6.17万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6481456
• 关键词: DNA binding protein; Drosophilidae; biological signal transduction; cell cell interaction; developmental genetics; gene expression; germ cells; immunocytochemistry; male; membrane proteins; mutant; phenotype; sperm; spermatogenesis; suppressor mutations; transcription factor

The incidence of testicular cancers and of male infertility is increasing. Insight into the cellular causes of this can only come with a systematic understanding of the regulatory pathways governing spermatogenesis. In order to generate functional sperm, several diverse cellular processes are coordinated during spermatogenesis. These processes include the growth and maturation of spermatocytes, which occurs in close association with surrounding somatic cells, suggesting that soma-germline communication is involved. This proposal focuses on spermatogenesis in Drosophila, which is similar to that in mammals, and in which genetic analysis provides a way to systematically dissect the signals necessary for spermatocyte development. The transcriptional activator Eyes absent (Eya) is expressed in somatic cyst cells where it is required for the maintenance of encysted spermatocytes. Sine oculis (So), a homeodomain protein that appears to act in a transcriptional regulatory complex with Eya, is also required for spermatocyte maintenance. The hypothesis to be tested is that an Eya/So-dependent signal from cyst cells is required for spermatocyte development. The role of Eya/So in cyst cell fate and behavior will be assessed. In addition, the stage at which Eya and So affect spermatocyte development will be defined. Next, the ectopic expression of Eya and So will test whether the Eya/So-dependent signal is permissive or instructive. Complementary approaches, including the analysis of 40 spermatocyte degeneration mutants and a genetic screen for suppressors, will attempt to identify the signal from somatic cells, or components of its response in spermatocytes.

睾丸癌和男性不育症的发生率正在增加。 对此细胞原因的洞察力只有对管理精子发生的调节途径有系统的理解。 为了产生功能性精子，精子发生过程中有几种不同的细胞过程。 这些过程包括与周围的细胞密切相关的精子细胞的生长和成熟，这表明涉及Soma-Germline通信。 该建议的重点是果蝇中的精子发生，果蝇类似于哺乳动物，其中遗传分析提供了一种系统地剖析精子发展所需的信号的方法。不存在转录激活剂眼（EYA）在体细胞细胞中表达，在这些细胞中维持经过环保精子细胞所必需的。 正弦Oculis（SO）是一种同源域蛋白，似乎在与EYA的转录调节复合物中作用，还需要用于维持精子细胞。 要测试的假设是，精子发育需要来自囊肿细胞的EYA/SO依赖性信号。 EYA/SO在囊肿细胞命运和行为中的作用将被评估。 另外，将定义EYA和因此影响精子发育的阶段。 接下来，EYA的异位表达，因此将测试EYA/SO依赖性信号是允许还是启发性的。 补充方法，包括对40个精子变性突变体的分析和抑制因子的遗传筛选，将试图鉴定来自体细胞的信号，或其在精子细胞中其反应的成分。