Control of Oocyte Maturation in C. elegans

卵母细胞减数分裂成熟是有性生殖所必需的。卵母细胞减数分裂成熟的定义是： 减数分裂终变期（减数分裂前期的最后阶段）和减数分裂中期之间的过渡， 伴随核膜破裂、皮质细胞骨架重排和减数分裂纺锤体 组装件.在许多物种中，激素通过调节CDK/细胞周期蛋白、MAP激酶和细胞周期蛋白来触发减数分裂成熟。 气体调节蛋白激酶A通路。性腺的体细胞也在调节 减数分裂成熟尽管如此，我们对细胞间信号如何控制减数分裂的认识仍有许多空白 并准备卵母细胞进行受精。鉴定了近端减数分裂信号， 在哺乳动物系统中具有挑战性，并且仍有待确定这些未表征的信号是如何被识别的。 接收并处理。在雌性减数分裂I中染色体的错误分离是导致 流产和唐氏综合症，最近的工作指出，在卵子发生过程中激素信号缺陷， 是人类非整倍体的重要原因。 我们实验室的工作已经建立了线虫秀丽隐杆线虫作为一个重要的系统， 研究卵母细胞减数分裂成熟信号。我们的研究表明C.精子出口 主要精子蛋白（MSP）通过囊泡出芽机制触发卵母细胞MAP激酶激活， 减数分裂成熟MSP还促进卵母细胞周围的卵泡样鞘细胞的收缩。 在前期的研究中，我们发现卵母细胞中的Eph/MSP受体通路和拮抗剂 鞘细胞中的Gao/i和Gas蛋白信号通路响应于 MSP。下一个资助期的主要目标将是阐明MSP的生物化学和细胞生物学 信号转导以解决卵母细胞和鞘细胞如何协调整合MSP减数分裂成熟信号。 为了实现这些目标，我们将：1）阐明MSP/VAB-1 Eph受体的分子决定簇 2）确定卵母细胞减数分裂成熟的MSP/Eph受体信号转导中内吞作用的作用;3） 确定性腺鞘细胞如何与VAB-1平行调节减数分裂成熟。以来 发育信号机制和细胞周期机制是进化保守的， 梭elegans模型系统将增强我们对人类生殖的理解。

Oocyte meiotic maturation is required for sexual reproduction. Oocyte meiotic maturation is defined by the transition between diakinesis (final stage of meiotic prophase) and metaphase of meiosis I and is accompanied by nuclear envelope breakdown, cortical cytoskeletal rearrangement, and meiotic spindle assembly. In many species, hormones trigger meiotic maturation by regulating CDK/cyclin, MAP kinase, and Gas-regulated protein kinase A pathways. Somatic cells of the gonad also play critical roles in regulating meiotic maturation. Still, there are many gaps in our knowledge of how intercellular signals control meiotic progression and prepare the oocyte for fertilization. Identification of the proximate meiotic signals has proved challenging in mammalian systems and it remains to be determined how these uncharacterized signals are received and processed. Chromosome missegregation in female meiosis I represents the leading cause of miscarriage and Down syndrome and recent work points to hormonal signaling deficits during oogenesis as a significant cause of aneuploidy in humans. Work in our laboratory has established the nematode Caenorhaditis elegans as an important system for studying oocyte meiotic maturation signaling. Our studies demonstrate that C. elegans sperm export the major sperm protein (MSP) by a vesicle budding mechanism to trigger oocyte MAP kinase activation and meiotic maturation. MSP also promotes the contraction of the follicle-like sheath cells that surround oocytes. In the prior funding period, we discovered that an Eph/MSP receptor pathway in the oocyte andantagonistic Gao/i and Gas protein signaling pathways in the sheath cells regulate meiotic maturation in response to MSP. Major goals for the next funding period will be elucidating the biochemistry and cell biology of MSP signaling to address how oocyte and sheath cells coordinately integrate the MSP meiotic maturation signal. To achieve these goals, we will: 1) Elucidate the molecular determinants of the MSP/VAB-1 Eph receptor interaction; 2) Define the role of endocytosis in MSP/Eph receptor signaling for oocyte meiotic maturation;3) Determine how the gonadal sheath cells regulate meiotic maturation in parallel to VAB-1. Since developmental signaling mechanisms and the cell cycle machinery are evolutionary conserved, studies in the C. elegans model system will enhance our understanding of human reproduction.