SOMATIC CELLS AND SPERMATOCYTE MAINTENANCE IN DROSOPHILA

果蝇体细胞和精母细胞的维持

• 批准号: 6054203
• 负责人: STEPHEN Francis DINARDO
• 金额: $ 23.52万
• 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/6054203
• 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增加。只有对精子发生的调控途径有了系统的了解，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，几个不同的细胞过程是协调的。这些过程包括精母细胞的生长和成熟，这些过程与周围的体细胞密切相关，表明体细胞-种系通讯参与其中。本研究的重点是果蝇的精子发生，这与哺乳动物的精子发生类似，遗传分析为系统地剖析精子细胞发育所需的信号提供了一种方法。转录激活因子Eyes absent （Eya）在体细胞包囊细胞中表达，在那里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，似乎在与Eya的转录调节复合体中起作用，也是维持精母细胞所必需的。需要验证的假设是，来自囊肿细胞的Eya/ so依赖性信号是精母细胞发育所必需的。我们将评估Eya/So在囊肿细胞命运和行为中的作用。此外，Eya和So影响精母细胞发育的阶段将被确定。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指导性的。互补的方法，包括对40个精子细胞变性突变体的分析和对抑制因子的遗传筛选，将试图识别来自体细胞的信号，或其在精子细胞中的反应成分。