成体肝脏表达多种肝脏特异或富集的基因，这些基因的缺陷往往会造成人类疾病。尽管目前人们对这类基因的生理功能已有了较多的了解，但对它们是否参与调控肝脏发育知之甚少。通过分析斑马鱼肝脏富集基因的基因芯片数据我们首次鉴定了新基因leg1。斑马鱼的leg1基因有两个拷贝leg1a和leg1b，它们在染色体上紧密连锁，并均在成体肝脏中富集表达。leg1编码一个全新的外分泌蛋白。我们最新的未发表的数据显示leg1a母源-合子突变体呈现生长环境依赖性小肝脏性状、Leg1蛋白分子存在糖基化和二硫键修饰，且leg1转录表达在斑马鱼和小鼠中均受饥饿诱导。本研究计划深入研究Leg1调控肝脏发育的机制、leg1蛋白分子修饰与其功能关系、Leg1在饥饿生理反应中的作用。研究成果不仅将极大地丰富肝脏早期发育的内涵，同时还有可能为饥饿生理学开辟新的研究方向。

The liver expresses a large number of liver-specific or -enriched genes which encode factors essential for the liver function. Loss-of-function of such genes often causes diseases in human. Although vast information has been obtained for these liver genes their roles in the early liver development are less studied. Based on analyzing the microarray data of liver-enriched genes in zebrafish we were the first to identify a novel gene leg1 (liver-enriched gene 1). Our further studies revealed that leg1 has two gene copies, leg1a and leg1b, which are closely linked to each other on chromosome 20. Both leg1a and leg1b were expressed in the adult liver. The leg1 gene encodes a novel secretory protein. Recently, our unpublished data showed that 1) loss of maternal and zygotic Leg1 protein resulted in a growth environment-dependent small liver phenotype in zebrafish; 2) we also found that Leg1 protein is modified by glycosylation and disulfide bond; 3) more interestingly, we found that the expression of leg1 can be iduced by starvation treatment in both zebrafish and mouse. Database search and sequence alignment showed that Leg1 evolutionally appears to be unique in the vertebrates, however, the function of Leg1 has not been well studied. Here we designed a detailed proposal to study the biological function of Leg1 including 1) the molecular mechanism of Leg1 in regulating liver development, 2) the relationship between Leg1 protein modification and liver development, and 3) the role of Leg1 during starvation response in zebrafish and mouse. We believe that the result obtained will no doubt extend our understanding of the process of liver development and the physiology of starvation response.