利用秀丽隐杆线虫研究温度对生殖腺性别决定的影响及分子机理

性别决定是决定动物发育方向的关键调控过程。温度如何调控性别决定是基本的生物学问题。温度被识别并转化为性别决定信号的机制一直未能解析。申请人的前期研究作出了阶段性突破：在雌雄同体秀丽隐杆线虫中，高温诱导生殖腺雄性化及内质网蛋白稳态波动；遗传分析证明内质网稳态影响性别决定信号通路，从而调控生殖腺的性别；在采用雌性/雄性生殖方式的线虫中，内质网稳态也能调控生殖腺的性别，暗示内质网稳态调控生殖细胞分化方向的功能在进化上是保守的。基于此，我们推测：内质网稳态关键性的介导了温度对生殖腺性别的调控作用。本研究拟以秀丽隐杆线虫为研究对象，进一步深入解析温度引发的内质网稳态波动的分子特征，阐明内质网稳态失衡促进生殖细胞向精细胞分化的细胞过程和分子机理。由于温度可通过影响蛋白折叠的能量状态影响内质网稳态，本项目可能解答温度如何被感知并转化为信号驱动性别转换，从而填补教科书中温度调控性别决定机制的空白。

Regulation of sex determination by temperature is an important and fundamental biological process. Sex determination regulates the sexual dimorphisms in both soma and the germ line. Because germline sex determination controls the decision between oocyte and sperm, it is important to understand the underlying mechanism. Since the initial discovery of temperature-dependent sex determination in turtles in 1966, the related mechanism is still not well known. Our preliminary study has made some significant progress, showing that high temperature treatment can induce masculinization of germline in the C elegans hermaphrodites. In addition, mild imbalance of ER proteostasis has been observed in these animals with high-temperature treatment. Furthermore, genetic analyses indicated that ER proteostasis is critically involved in the germline sex determination. Finally, ER proteostasis also functions in the male/female species, C remanei, implying the role of ER proteostasis is evolutionary conserved. Therefore, we hypothesized that ER proteostasis criticically mediates the impact of temperature on the germ cell fate. In this study, we will use C elegans as a model system to understand the changes in the imbalance of ER proteostasis that induced by high-temperature treatment, and to elucidate the mechanism that mild imbalance of ER proteostasis promote the male cell fate in the germline. Since ambient temperature can directly affect the folding of proteins by altering the energetic status, this study could unveil that ER proteostasis can perceive the change of temperature and in turn, regulates the activities of the germline sex determination pathway. This could be the first study to identify the molecular basis that responds to temperature and then transduce it into signal of sex alteration.