Relationship between asymmetric nodal expression and the direction of embryonic turning.

Growth factors related to TGF-beta provide important signals for patterning the vertebrate body plan. One such family member, nodal, is required for formation of the primitive streak during mouse gastrulation. Here we have used a nodal-lacZ reporter allele to demonstrate asymmetric nodal expression in the mouse node, a structure thought to be the functional equivalent of the frog and chick 'organizer', and in lateral place mesoderm cells. We have also identified two additional genes acting with nodal in a pathway determining the left-right body axis. Thus we observe in inv mutant embryos that the sidedness of nodal expression correlates with the direction of heart looping and embryonic turning. In contrast, HNF3-beta(+/-) nodal(lacZ/+) double-heterozygous embryos display LacZ staining on both left and right sides, and frequently exhibit defects in body situs. Taken together, these experiments, along with similar findings in chick, demonstrate that elements of the genetic pathway that establish the left-right body axis are conserved in vertebrates.