The regulation of cell differentiation and morphogenesis on mamalian early development

lefty-1和lefty-2基因都在发育中的小鼠胚胎的左侧表达，并与左右（L-R）轴的形成有关。随着转基因分析的使用，这些基因的转录调控区负责他们的L-R不对称表达现在已经调查。lefty-1的9.5kb上游区和lefty-2的5.5kb上游区再现了相应基因的表达模式。缺失结构的检查揭示了左侧特异性增强子（ASE）的存在，这是必需的和足够的lefty-2不对称表达。相反，leftty-1的不对称表达被证明是由双侧增强子和右侧特异性沉默子（RSS）的组合决定的。lefty-1和lefty-2的9.5kb区域分别与lefty-1和lefty-2的上游基因iv和inv反应。iv和inv对lefty-2的调节作用均由ASE介导。这些结果表明，尽管左撇子-1和左撇子-2之间的相似性，不同的调控机制的基础上，他们的不对称表达。

Both lefty-1 and lefty-2 genes are expressed on the left side of developing mouse embryos and are implicated in left-right (L-R) axis formation. With the use of transgenic analysis, the transcriptional regulatory regions of these genes responsible for their L-R asymmetric expression have now been investigated. The 9.5-kb upstream region of lefty-1 and the 5.5-kb upstream region of lefty-2 reproduced the expression pattern of the corresponding gene. Examination of deletion constructs revealed the presence of a left side-specific enhancer (ASE) that is essential and sufficient for lefty-2 asymmetric expression. In contrast, the asymmetric expression of lefty-1 was shown to be determined by a combination of bilateral enhancers and a right side-specific silencer (RSS). The 9.5-kb region of lefty-1 and the 5.5-kb region of lefty-2 responded to iv and inv, upstream genes of lefty-1 and lefty-2. The regulation of lefty-2 by iv and inv was mediated by ASE. These results suggest that, in spite of the similarities between lefty-1 and lefty-2, different regulatory mechanisms underlie their asymmetric expression.