ZFP568与IGF2在植入后胚胎中的发育生物学研究

胚胎着床及早期胚胎发育中的分子调控网络是当前胚胎医学和发育生物学研究的重点。锌指蛋白ZFP568在小鼠基因组上专一性调控胚胎发育关键生长激素IGF2胎盘特异转录本的表达活性，其通过专一性抑制IGF2的转录活性，在原肠胚形成阶段发挥关键作用。然而，ZFP568如何通过IGF2影响原肠胚形成的作用机制仍不清楚。本项目拟从发育角度入手，充分运用多种胚层/细胞特异性Cre酶的转基因/基因敲入小鼠模型，采用微量细胞组学分析、原位杂交及CRISPR/Cas9等多种技术手段，深入研究植入后胚胎发育、尤其是原肠胚形成过程中ZFP568与IGF2对小鼠胚胎发育的影响。同时分析IGF2下游细胞通讯与信号通路，探索胚外组织信号对胚胎细胞发育的重要影响。本项目的研究将深入理解植入后发育过程中胚胎细胞与胚外组织之间的分子调控网络，对早期胚胎发育中胚胎异常等临床疾病机制的理解提供强有力的理论基础。

Molecular regulatory networks in implantation and early embryonic development represent trends of current research on embryonic medicine and developmental biology. KRAB-Zinc finger protein ZFP568, which plays a key role in gastrulation during early embryonic development, specifically regulates the transcriptional activity of a placental-specific transcript of the insulin-like growth factor 2 (IGF2). However, the mechanisms involved in this process remain poorly understood. By using in situ hybridization, CRISPR/Cas9 and small-scale high-throughput sequencing profiling, combined with the construction of numerous transgenic and knockout mouse models, this project intends to illustrate the functions and mechanisms of ZFP568-IGF2 during mouse post-implantation development, especially gastrulation stage. Meanwhile, by analyzing the cellular communications and signaling pathways downstream of IGF2, this project tries to explore the important effects of extra-embryonic signals. In summary, our study will shed light on the molecular regulatory network between embryonic cells and the extra-embryonic tissues during post-implantation development, thus providing a strong theoretical basis for the mechanical understanding of diseases such as embryonic defects during early development.