Distinct transcriptional regulatory mechanisms underlie left-right asymmetric expression of lefty-1 and lefty-2

Both lefty-1 and lefty-2 genes are expressed on the left side of developing mouse embryos and are implicated in left-right (GR) axis formation. With t he use of transgenic analysis, the transcriptional regulatory regions of th ese genes responsible for their GR asymmetric expression have Plow been inv estigated. The 9.5-kb upstream region of lefty-1 and the 5.5-kb upstream re gion of lefty-2 reproduced the expression pattern of the corresponding gene . Examination of deletion constructs revealed the presence of a left side-s pecific enhancer (ASE) that is essential and sufficient for lefty-2 asymmet ric 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, di fferent regulatory mechanisms underlie their asymmetric expression.