肌肉发育是早期发育重要事件，选择性剪切及其调控的剪切事件在其中起重要作用。选择性剪切因子SRSF10通过调控LRRFIP1在肌肉发育过程起作用。LRRFIP1是一个具有多转录本的多功能蛋白，但功能研究集中在体外，不同转录本在体内的功能几乎是空白。我们前期研究发现斑马鱼中两个LRRFIP1的同源基因的部分剪切体特异表达在体节中，表明与肌肉发育有关。基于此，将1）首先确定这两个基因在早期体节特异表达的剪切体形式、早期表达模式及亚细胞定位。2）利用基因敲除等手段，研究它们在肌肉前体细胞形成、肌细胞增殖、凋亡和分化中的具体作用。3）并探索其作用机制，确定其是否为肌肉分化相关的抑制因子；是否调控Wnt信号通路；鉴定与肌肉细胞特异表达LRRFIP1剪切体相互作用的蛋白质，完善肌肉发育的基因调控网络。研究结果有助于阐明LRRFIP1 在肌细胞发育中的功能和和作用机理，为肌肉/心肌相关疾病提供理论基础。

Alternative splicing and the regulated splicing event are critical to muscle development. Splicing factor SRSF10 is important to muscle development by regulating LRRFIP1. Lrrfip1 is an interesting gene with different spliced form, however, the research is mainly focused in vitro, the research of spliced forms in vivo is lacking. We found that the two zebrafish homologues of lrrfip1(lffrip1a and lffrip1b) are strongly expressed in muscle cells, knockdown of these two genes results in muscle defects in early embryos. We plan to 1) determine the spliced form of lrrfip1a/b in somite and describe in detail the expression pattern of lrrfip1a/b genes and the subcellular localization of LRRFIP1a/b in zebrafish embryo.2) to investigate their implication in muscle cell formation, differentiation, stability and integrity using knockdown or knockout approaches in zebrafish. 3) explore the possible mechanisms. We will try first to determine the transcriptional repressor activity, then to determine its regulation of Wnt/β-catenin pathway, In addition, we will identify the partners of LRRFIP1a/b using yeast two hybrid and co-immunoprecipitation approaches. The function of these LRRFIP1-interacting proteins in embryonic muscle cells will be analyzed in order to understand how LRRFIP1a/b protein complex regulates muscle development. These analyses should provide a mechanistic insight into the implication of LRRFIP1a/b protein complex in the regulation of muscle function. They should also help to identify other molecules involved in muscular defect, and thus lead to a better understanding of the pathogenesis of musclular diseases.