Relationship between asymmetric nodal expression and the direction of embryonic turning

Abstract

GROWTH factors related to TGF-β provide important signals for patterning the vertebrate body plan^1–3. One such family member, nodal, is required for formation of the primitive streak during mouse gastrulation^4–6. 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'⁷, and in lateral plate 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 embryos⁸ that the sidedness of nodal expression correlates with the direction of heart looping and embryonic turning. In contrast, HNF3-β^+/- 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 chick⁹, demonstrate that elements of the genetic pathway that establish the left–right body axis are conserved in vertebrates.