Cell Signaling in Meiosis

描述（由申请方提供）：配子发生对于所有有性生殖生物的繁殖至关重要，包括通过减数分裂使染色体数目减半，以及随后将单倍体产物包装成配子（哺乳动物中的精子和卵子）。减数分裂和配子形成必须紧密结合，以确保形成有活力的后代;干扰导致不育，不活力和出生缺陷。毫不奇怪，大量的信号分子参与精确调节这种细胞分化程序。在酿酒酵母中，有性生殖通过孢子形成发生，在许多方面与哺乳动物的配子发生相似。我们已经表明，保守的信号分子磷脂酶D（PLO）和Ste 2 O样激酶，Sps 1是必不可少的酵母孢子形成，但他们在这一过程中的确切作用在很大程度上是unknow.We建议继续利用酵母的遗传学，以阐明参与调节孢子形成的细胞分化程序的信号通路。我们将使用三管齐下的方法来分析PLO和Sps 1的作用：1）我们将研究在孢子形成中对PLO产生的脂质的具体要求。2)我们将阐明一个发育调节的艺术GAP的功能，并确定它是否介导PLO途径的功能。3)我们将研究PLD和Sps 1之间的关系，并确定Sps 1信号通路的其他组件。总之，我们的研究将提供一个框架，了解细胞信号事件是如何协调，以确保形成可行的后代。鉴于这些分子之间广泛的进化保守程度，这是可能的，PLD和Sps 1在酵母枯萎病的功能的理解提供了一般的见解orthopathy分子在人类中的作用，其改变的调节不育症，出生缺陷和疾病的后果。

DESCRIPTION (provided by applicant): Gametogenesis is essential for the propagation of all sexually reproducing organisms and consists of halving the chromosome number through meiosis, and the subsequent packaging of the haploid products into gametes (sperm and eggs in mammals). Meiosis and gamete formation must be tightly coupled to ensure the formation of viable progeny; perturbations result in infertility, inviability and birth defects. Not surprisingly, a large number of signaling molecules participate in precisely regulating this cellular differentiation program. In the yeast Saccharomyces cerevisiae, sexual reproduction occurs via sporulation and is similar in many respects to gametogenesis in mammals. We have shown that the conserved signaling molecules Phospholipase D (PLO) and the Ste2O-like kinase, Sps1 are essential for yeast sporulation, but their precise roles in this process are largely unknown.We propose to continue to exploit the genetics of yeast to elucidate the signaling pathways involved in regulating the cellular differentiation program of sporulation. We will analyze the role of PLO and Sps1 using a three-pronged approach: 1) we wilt investigate the specific requirement for PLO-generated lipids in sporulation. 2) We will elucidate the function of a developmentally regulated Art-GAP and determine if it mediates PLO pathway function. 3) We will examine the relationship between PLD and Sps1 and identify additional components of the Sps1 signaling pathway. Taken together, our studies will provide a framework for understanding how cell signaling events are coordinated to ensure the formation of viable progeny. Given the extensive degree of evolutionary conservation between these molecules, it is likely that an understanding of the function of PLD and Sps1 in yeast wilt provide general insights into the role of orthologous molecules in humans and the consequences of their altered regulation in infertility, birth defects and disease.