Control of Onset of Meiosis in C. elegans

描述（由申请人提供）：本项目的长期目标是了解控制生殖细胞增殖和减数分裂进入的体细胞-生殖细胞相互作用的分子基础。在人类中，不育可能是由于生殖细胞增殖不足或发育或激素异常干扰配子产生或功能。生殖系恶性肿瘤可由保留或重新获得有丝分裂潜能的生殖细胞过度增殖引起。在许多动物中，早期生殖系扩增发生在发育中的体细胞性腺内，并且索马和生殖系之间的通信确保了它们的协调发育。相对容易的分子/遗传学解剖控制生殖细胞扩增和减数分裂进入一个简单的动物，如C。elegans将帮助我们理解这个过程的一般。最近的研究结果表明，不同的细胞在C。线虫雌雄同体体细胞性腺鞘谱系影响（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形成。该提案旨在阐明这些相互作用的分子基础，通过对已知的突变体进行分子/遗传分析，模拟去除所涉及的体细胞的效果，并通过使用区分体细胞和种系自主活动的反向遗传方法进行全基因组遗传筛选。

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.