NODAL-RELATED SIGNALS INDUCE AXIAL MESODERM AND DORSALIZE MESODERM DURING GASTRULATION

Mouse embryos homozygous for a null mutation in nodal arrest developme nt at early gastrulation and contain little or no embryonic mesoderm. Here, two Xenopus nodal-related genes (Xnr-1 and Xnr-2) are identified and shown to be expressed transiently during embryogenesis, first wit hin the vegetal region of late blastulae and later in the marginal zon e during gastrulation, with enrichment in the dorsal lip. Xnrs and mou se nodal function as dose-dependent dorsoanterior and ventral mesoderm inducers in whole embryos and explanted animal caps. Using a plasmid vector to produce Xnr proteins during gastrulation,,ve show that, in c ontrast to activin and other TGF beta-like molecules, Xnr-1 and Xnr-2 can dorsalize ventral marginal zone explants and induce muscle differe ntiation, Xnr signalling also rescues a complete embryonic axis in UV- ventralized embryos. The patterns of Xnr expression, the activities of the proteins and the phenotype of mouse nodal mutants, all argue stro ngly that a signaling pathway involving nodal, or nodal-related peptid es, is an essential conserved element in mesoderm differentiation asso ciated with vertebrate gastrulation and axial patterning.