Control of Onset of Meiosis in C. elegans

描述(由申请人提供)：这个项目的长期目标是了解控制生殖系增殖和减数分裂进入的体细胞-生殖系相互作用的分子基础。在人类中，不育可能是生殖细胞增殖不足，或者是干扰配子产生或功能的发育或激素异常造成的。生殖系恶性肿瘤可能是由于保持或重新获得有丝分裂潜能的生殖细胞过度增殖所致。在许多动物中，早期的生殖系扩增发生在发育中的体细胞性腺中，体细胞和生殖系之间的沟通确保了它们的协调发展。对像线虫这样的简单动物生殖系扩增和减数分裂进入的控制进行相对简单的分子/遗传解剖将有助于我们从总体上理解这一过程。最近的研究结果表明，线虫雌雄同体的不同细胞对(1)生殖系扩增和减数分裂进入的时空控制以及(2)不适当的生殖系肿瘤的形成有影响。这一建议旨在通过对模仿去除相关体细胞的影响的已知突变体的分子/遗传分析，以及通过使用区分体细胞和生殖系自主活动的反向遗传方法进行全基因组遗传筛选，来阐明每一种相互作用的分子基础。

DESCRIPTION (provided by applicant): The long-term objective of this project is to understand the molecular basis for soma-germline interactions that govern germline proliferation and meiotic entry. In humans, sterility can result from insufficient proliferation of germ cells or from developmental or hormonal abnormalities that interfere with gamete production or function. Germline-based malignancy can result from over-proliferation of germ cells that retain or re-acquire mitotic potential. In many animals, early germline amplification occurs within the developing somatic gonad, and communication between the soma and germ line ensures their coordinate development. The relatively facile molecular/genetic dissection of the control of germline amplification and meiotic entry in a simple animal such as C. elegans will aid our understanding of this process in general. Recent results indicate that distinct cells in the C. elegans hermaphrodite somatic gonadal sheath lineage influence (1) germline amplification and spatio-temporal control of meiotic entry and (2) inappropriate germline tumor formation. This proposal aims to elucidate the molecular basis for each of these interactions by molecular/genetic analysis of known mutants that mimic the effect of removal of the somatic cells involved, and by genome-wide genetic screening using reverse-genetic methods that distinguish between somatic-and germline-autonomous activities.