囊胚中Hippo信号通路的调控机制的研究

The Hippo pathway plays an essential role in regulating the differentiation of the inner cell mass and the trophectoderm during blastocyst formation. However, how the Hippo pathway is differentially regulated in the blastocyst, has not been well understood. Using a chemical library with known biological functions, we screened for regulatory factors of the Hippo pathway in the blastocyst, and identified three candidate factors, including Rho GTPases, affecting the subcellular distribution of YAP in the blastocyst. We will further characterize the function of these factors in early embryogenesis, elucidate the novel mechanism for Rho GTPases to regulate the Hippo-YAP pathway independent of cell polarity and cell skeleton, and study the molecular mechanisms how two other factors regulate the Hippo-YAP pathway. Our studies will shed light on the molecular mechanism of early embryogenesis, as well as pluripotency establishment and maintenance, thus, benefiting the prevention of spontaneous abortion and improving the reproduction efficiency.

Hippo信号通路在调控囊胚中内细胞团和滋养层细胞的分化中起重要作用。但是，囊胚中Hippo信号通路的调控机制仍未被阐明。本课题应用一个具有生物学活性的化合物文库筛选囊胚中Hippo的调控因子，已找出了包括Rho GTPases在内的3个在囊胚中调控Hippo-YAP通路的因子。在此基础上，进一步研究这些调控因子对胚胎发育的影响，并探讨Rho GTPases不依赖于细胞极性和细胞骨架来调控Hippo-YAP通路的新机制，以及其它两个调控因子的作用机制。我们的研究将加深对胚胎发育以及建立和维持发育多能性的分子机制的理解，对防止自然流产和提高繁殖的成功率有重要的现实意义。

Hippo信号通路在调控囊胚中内细胞团和滋养层细胞的分化中起重要作用。但是，囊胚中Hippo信号通路的调控机制仍未被阐明。本课题应用一个具有生物学活性的化合物文库筛选囊胚中Hippo的调控因子，发现Rho在滋养层细胞中抑制Hippo信号，而PKA则在内细胞团中激活Hippo。我们进一步阐明了Rho通过阻止Amot和Nf2之间的相互作用来抑制Hippo信号的机制。本课题的成果加深了对胚胎发育以及建立和维持发育多能性的分子机制的理解，对防止自然流产和提高繁殖的成功率有重要的现实意义。.此外，我们还阐明了Cops2、Cops5在胚胎干细胞自我更新、基因组稳定性维持中的作用和机制。