LEFTY-1 IS REQUIRED FOR LEFT-RIGHT DETERMINATION AS A REGULATOR OF LEFTY-2 AND NODAL

lefty-1, leffy-2 and nodal are expressed on the left side of developin g mouse embryos and are implicated in left-right (L-R) determination. The role of lefty-1 was examined by analyzing mutant mice lacking this gene. The lefty-1-deficient mice showed a variety of L-R positional d efects in visceral organs. Unexpectedly, however, the most common feat ure of lefty-1(-/-) mice was thoracic left isomerism (rather than righ t isomerism). The lack of lefty-1 resulted in bilateral expression of nodal, lefty-2, and Pitx2 (a homeobox gene normally expressed on the l eft side). These observations suggest that the role of lefty-1 is to r estrict the expression of lefty-2 and nodal to the left side, and that lefty-2 or nodal encodes a signal for ''leftness.''