Drosophila melanogaster p53 during gonadogenesis

性腺发生过程中的果蝇 p53

• 批准号: 6552596
• 负责人: MATTHEW J WAWERSIK
• 金额: $ 3.83万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6552596
• 关键词: DNA damage; Drosophilidae; X ray; apoptosis; cell cycle; cell proliferation; confocal scanning microscopy; embryogenesis; fluorescent in situ hybridization; gametogenesis; gonads; green fluorescent proteins; p53 gene /protein; postdoctoral investigator; protein structure function; reproductive development; terminal nick end labeling

DESCRIPTION (provided by applicant): Germline development is a highly evolutionarily conserved process, which, ultimately, gives rise to either sperm or eggs. One potential regulator of this process is the tumor suppressor gene p53. During gametogenesis, it has been proposed that p53 functions in surveillance of germ cells by mediating apoptosis and cell cycle arrest. In addition, it has been recently reported that the Drosophila homolog of p53 (Dmp53) is expressed in germ cells prior to the onset of gametogenesis. This expression pattern is consistent with that seen in organisms ranging from clams to humans. Therefore, we propose that p53 may also perform a role in germline surveillance during earlier stages of development to test this hypothesis, we intend to use Drosophila Melanogaster, as a model system to study the role of p53 during early germ cell development. Specifically, we will undertake (1) a thorough characterization of Dmp53 expression during germline development, including an analysis of somatic cues regulating its expression, (2) an analysis of Dmp53's impact on apoptosis, cell cycle progression and germ cell maturation during germline development, and (3) an examination of Dmp53's ability to directly mediate germline surveillance. Together, these studies will provide insight into the role of Dmp53 during germ cell development and germline selection.

描述（由申请人提供）：生殖系发育是一个高度进化保守的过程，最终产生精子或卵子。这一过程的一个潜在调节因子是肿瘤抑制基因p53。在配子发生过程中，已经提出p53通过介导细胞凋亡和细胞周期停滞来监视生殖细胞。此外，最近有报道说，果蝇同源的p53（Dmp53）的生殖细胞中表达的配子发生之前的开始。这种表达模式与从蛤到人类的生物体中所见的一致。因此，我们提出，p53也可能在生殖细胞的早期发育阶段的监督执行的作用，以测试这一假设，我们打算使用果蝇，作为一个模型系统来研究p53在早期生殖细胞发育的作用。具体而言，我们将进行（1）在生殖系发育过程中Dmp53表达的彻底表征，包括调节其表达的体细胞信号的分析，（2）在生殖系发育过程中Dmp53对细胞凋亡，细胞周期进程和生殖细胞成熟的影响的分析，以及（3）Dmp53直接介导生殖系监视的能力的检查。总之，这些研究将为Dmp53在生殖细胞发育和种系选择过程中的作用提供深入了解。