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病率正在上升。只有系统地了解精子发生的调控途径，才能深入了解这一现象的细胞原因。为了产生有功能的精子，在精子发生过程中需要协调几个不同的细胞过程。这些过程包括精母细胞的生长和成熟，这与周围的体细胞密切相关，这表明体细胞-生殖系通讯参与了这一过程。这一建议的重点是果蝇的精子发生，这类似于哺乳动物的精子发生，其中遗传分析提供了一种系统地剖析精母细胞发育所需信号的方法。转录激活因子Eya在体细胞囊细胞中表达，它是维持包囊精母细胞所必需的。Sine Oculis(SO)是一种同源结构域蛋白，似乎与Eya在转录调控复合体中发挥作用，也是维持精母细胞所必需的。要检验的假设是，精母细胞的发育需要来自囊细胞的Eya/So依赖信号。Eya/So在囊性细胞命运和行为中的作用将被评估。此外，还将确定Eya等影响精母细胞发育的阶段。接下来，Eya和So的异位表达将测试Eya/So依赖信号是允许的还是具有启发性的。辅助性方法，包括对40个精母细胞退化突变的分析和对抑制子的遗传筛选，将试图识别来自体细胞的信号，或精母细胞中的反应成分。