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增加。 只有系统地了解精子发生的调控途径，才能深入了解其细胞原因。 为了产生有功能的精子，在精子发生过程中协调了几种不同的细胞过程。 这些过程包括精母细胞的生长和成熟，其发生与周围的体细胞密切相关，表明涉及体体-种系通讯。 该提案的重点是果蝇的精子发生，这与哺乳动物的精子发生相似，其中遗传分析提供了一种系统剖析精母细胞发育所需信号的方法。转录激活因子 Eyes Absent (Eya) 在体细胞囊肿细胞中表达，是维持包囊精母细胞所必需的。 眼正弦 (So) 是一种同源域蛋白，似乎与 Eya 一起在转录调节复合物中发挥作用，也是精母细胞维持所必需的。 要测试的假设是精母细胞发育需要来自囊肿细胞的 Eya/So 依赖性信号。将评估 Eya/So 在囊肿细胞命运和行为中的作用。 此外，还将确定 Eya 和 So 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 依赖性信号是允许的还是指导性的。 补充方法，包括对 40 个精母细胞变性突变体的分析和抑制因子的遗传筛选，将尝试识别来自体细胞的信号，或其在精母细胞中的反应成分。