母源复合体SCMC调控哺乳动物卵母细胞向早期胚胎转换的分子机制

母源调控主导早期胚胎发育,目前对哺乳动物母源调控认知非常有限。近期申请人新发现了哺乳动物卵母细胞和早期胚胎特异复合体SCMC (subcortical maternal complex)。该复合体包括多种母源蛋白，通过多种生物学事件调控卵母细胞向早期胚胎转变过程；编码该复合体的多种组分基因突变与女性生殖疾病发生密切相关，并形成哺乳动物母源调控领域的新方向。目前有关SCMC组成、分子功能及其作用机制还很不清楚。申请人准备利用生物化学、结构生物学和遗传学等的技术，鉴定SCMC新组分并研究其功能，解析SCMC组分蛋白质、复合体结构和蛋白质直接的作用关系，研究SCMC与胞质晶格及RNA的关系，探索SCMC基因突变动物模型在女性相关生殖疾病研究中的应用，最终揭示SCMC在哺乳动物卵母细胞向早期胚胎转变过程中的分子作用机制，为女性复发性早期胚胎丢失和胎儿印记基因异常等生殖疾病的预防和诊断提供新思路。

Maternal effect genes play essential roles in early embryogenesis before zygotic genome activation (ZGA). Using mouse genetic approach combined with biochemistry analysis, we have recently identified a mammalian-specific subcortical maternal complex (SCMC) that is essential for mouse preimplantation development. The SCMC includes several maternal proteins and is involved in multiple processes during mammalian oocyte-to-embryo transition. The mutation of human several SCMC genes is associated with certain human reproductive disorders. Currently, the constitution，the molecular function and the mechanism of SCMC remain largely unclear. Through biochemistry, structure biology and genetic approaches, we will identify the novel components of the SCMC, study the function of these new genes, illustrate the interaction of proteins in the SCMC, investigate the relationship between the SCMC and RNA and CPLs (cytoplasmic lattices) in this project. The mechanism of SCMC during mammalian oocyte-to-embryo transition may provide important insight to causes of human infertility and recurrent spontaneous abortions.