FUNCTIONAL DIFFERENCES AMONG XENOPUS NODAL-RELATED GENES IN LEFT-RIGHT AXIS DETERMINATION

An association has been noted previously in chick, mouse and frog embr yos between asymmetric nodal-related gene expression and embryonic sit us, implying an evolutionarily conserved role in left-right specificat ion, Of the four Xenopus nodal-related genes expressed during gastrula tion, only Xnr-1 is re-expressed unilaterally in the left lateral plat e mesoderm at neurula/tailbud stages, Here, we show that the asymmetri c expression of Xnr-1 can be made bilaterally symmetric by right-sided microinjection of RNA encoding active Xenopus hedgehog proteins, More over, we provide the first evidence that Xnr-1 expression per se is a causal factor in left-right axis determination, When plasmids expressi ng Xnr-1 were delivered unilaterally to the right side of Xenopus embr yos, a reversed laterality of both the heart and gut (homotaxic revers al) was induced in 40% of surviving embryos, while an additional 10-20 % showed reversal of the heart or gut alone (heterotaxia), This effect on laterality was specific to Xnr-1, since neither Xnr-2 nor Xnr-3 pl asmids had this activity, In addition, me find that Xnr-1 and Xnr-2, w hich have both been defined as mesoderm inducers from overexpression s tudies, show quantitative differences in their ability to induce dorsa l mesoderm, Together, these findings suggest that the various Xnrs per form substantially different functions during Xenopus embryogenesis. M oreover, they strongly support the hypothesis that left lateral plate expression of nodal-related genes is a causative factor in the determi nation of asymmetry in vertebrate embryos.