相分离描述了物质一种去混合的状态变化。近年来，相分离领域帮助打开了生命科学领域新的大门，为探索生物分子“高维”结构和功能提供了全新的思路。越来越多的研究表明，液-液相分离（LLPS）在生物体内存在并发挥功能，相分离的失调与蛋白聚集相关的人类疾病如肌萎缩侧索硬化（ALS）等密切相关。能触发液-液相分离过程的蛋白质具有内部无序区域（IDRs），目前对IDRs在体外发生相分离的调控机制研究较多，然而在胚胎发育过程中特定的IDRs通过相分离发挥着怎样的功能尚不清楚。申请人的前期发现了一个调控胚胎早期发育的重要因子Rbm14，它具有IDR，在胚胎合子基因组激活（ZGA）前后伴随着液-液相分离的现象，Rbm14的缺失会导致胚胎死亡。本项目将在前期研究基础上，以斑马鱼与小鼠为研究模型，结合体外和小鼠胚胎干细胞系统，深入研究并揭示Rbm14及其相分离在胚胎发育中的功能，阐明其发挥作用的分子机理。

Phase separation describes the process of a demixing transition. Recent discoveries have shed light on the higher dimension of biological macro-molecular structures and functions regulated by proteins liquid-liquid phase separation（LLPS）. Researches continuously reveal that LLPS participates in many biological processes, including forming the canonical membraneless organelles, signaling complexes, cytoskeletons and macromolecular complexes. Dysregulation of phase separation leads to aggregated-proteins-related disease such as amyotrophic lateral sclerosis(ALS). Proteins with intrinsically disordered regions (IDRs) can trigger LLPS. Although amino acids features and properties of IDRs have been studied, to what extent specific IDRs contribute to development via LLPS is however unknown. We uncovered a new embryonic regulator in zebrafish and mouse, the IDR-containing RNA-binding protein Rbm14, goes through LLPS around the zygotic genome activation(ZGA) process. Knockdown of Rbm14 results in early embryonic death. To further understand the mechanism of Rbm14 regulation in embryonic development by LLPS, we will use zebrafish and mouse as the research model, combined with in vitro and mouse embryonic stem cells system, to shed a fresh light on proteins LLPS regulation of embryonic development.