黄鳝肌肉生长抑制因子Myostatin信号途径相关基因的鉴定及调控网络分析

Myostatin (MSTN, also named GDF-8), a member of the tumour growth factor-β family, is a potent inhibitor of skeletal muscle growth. Deficiency of the MSTN gene will induce a dramatic increase in muscle mass, caused by a combination of hypertrophy and hyperplasia. Because of its role in the regulation of muscle growth, potential applications in aquaculture have been considered, and many MSTN sequences have been isolated from diverse fish species. However, little is known about the molecular mechanism of inhibition of muscle growth by MSTN, and many genes in MSTN regulation pathway remains poorly understood. Therefore, it is really necessary to discover genes related to MSTN regulation pathway and study the expressions and regulation mechanism. In this study, genes in MSTN regulation pathway will be studied from rice-field eel, a commercially important fish species. First, the 5' upstream sequence of MSTN will be analyzed to find potential transcription factors(upstream regulation genes) by bioinformatics method. Meanwhile, high-throughput sequencing will be used to screen the downstream effect genes of MSTN. Then, all these genes, including the upstream regulation genes and the downstream effect genes, will be confirmed with in vitro and in vivo methods. Basing on these results, the expressions and regulations of these genes will be studied. Also, we will analyze the regulation pathways on which these genes might be, and try to integrate relevant pathways so as to understand the MSTN regulation pathways deeply.

Myostatin（MSTN），即肌肉生长抑制因子，是肌肉生长的负调控因子，起着抑制肌肉细胞增殖和生长的作用。MSTN基因的功能缺失，将导致肌肉组织发生肥大与增生, 从而导致肌肉重量的增加。目前，在多种鱼类中都已克隆了许多MSTN基因。然而，人们对其作用机制依然缺乏足够的了解，MSTN调控途径上的许多基因仍然未知。因此，对MSTN调控途径的相关基因进行深入发掘，研究其表达调控机理则显得尤为必要。基于以上原因，我们以淡水鱼类--黄鳝作为研究对象，一方面，通过对其MSTN基因的5'上游序列进行生物信息学分析，鉴定其转录调控因子；另一方面，利用高通量测序技术对MSTN调控的下游基因进行转录组测序，筛选其下游效应基因。同时，对得到的上下游基因利用细胞和动物实验加以验证。并在此基础上，研究这些基因的表达调控及其所涉及的信号途径，通过整合相关的信号通路，以期对MSTN调控网络有一个深入的理解。