Polarity and meiotic exit in the early C. elegans embryo

描述(申请人提供)：线虫线虫的前后(A-P)体轴极化发生在受精后不久和第一轮有丝分裂开始之前。这种极化事件在卵母细胞染色体完成减数分裂后相继发生。有趣的是，减数分裂完成和轴线极化都是由精子的信号触发的，尽管很少有精子提供的因素被识别出来。最近的研究表明，减数分裂退出缺陷往往与轴建立缺陷相关，这表明这两个过程可能是发育相关的。尽管如此，对于这些事件如何在细胞内进行时间调控，或者两者之间可能的相互关系，我们知之甚少。为了研究这个问题，我们将研究线虫的SCU-1(精子提示异常)基因。SCU-1的突变导致减数分裂退出缺陷和A-P轴极化失败。此外，SCU-1基因产物来自母亲和父亲，这可能会导致更好地理解父亲提供的蛋白质。 为了揭示SCU-1调节陨石出射和轴极化的机制，研究将集中在三个具体目标上。1)通过检测SCU-1在MAPK和MPF减数分裂失活中的作用，以及通过解剖SCU-1在减数分裂过程中母本和父本的贡献，来研究SCU-1在减数分裂退出过程中的作用。2)SCU-1基因的分子同源性和蛋白的亚细胞定位将通过分子克隆和抗体产生及染色来确定；3)SCU-1相互作用的蛋白将通过基因抑制筛选和全基因组RNA干扰筛选来鉴定。这些研究应该为控制早期胚胎细胞周期和极性协调的机制提供洞察力。

DESCRIPTION (provided by applicant): Polarization of the anterior-posterior (A-P) body axis in the nematode Caenorhabditis elegans occurs shortly after fertilization and before onset of the first round of mitosis. This polarization event occurs in close succession following the completion of meiosis by the oocyte chromosomes. Interestingly, both meiotic completion and axis polarization are triggered by cues from the sperm, although very few sperm-supplied factors have been identified. Recent studies have suggested that meiotic exit defects often correlate with defects in axis establishment, suggesting that these two processes may be developmentally linked. Despite this, little is known about how these events are temporally regulated in the cell or possible interrationships between the two. To investigate this problem, the scu-1 (sperm cue abnormal) gene will be studied in C. elegans. Mutations in scu-1 result in both a meiotic exit defect and a failure to polarize the A-P axis. In addition, the scu-1 gene product is contributed both maternally and paternally which may lead to a better understanding of paternally supplied proteins. To uncover the mechanisms by which scu-1 regulates meioitic exit and axis polarization, research will focus on three specific aims. 1) The role of scu-1 during meiotic exit will be examined by testing the role for scu-1 in MAPK and MPF deactivation after meiosis, and by dissecting the maternal and paternal contributions of SCU-1 during meiosis. 2) The molecular identity of the scu-1 gene and the subcellular localization of the protein will be determined through molecular cloning and antibody production and staining 3) SCU-1 interacting proteins will be identified though genetic suppressor screens and a genome-wide RNA interference screen for enhancers. These studies should provide insights into the mechanisms controlling the coordination of the cell cycle and polarity in the early embryo.