Mutation of the mouse nodal gene, a member of the TGF-beta superfamily, causes embryonic arrest prior to mesoderm formation. Studies performed in amphibians suggest that nodal is a mesoderm inducing factor. Nodal may also have an important role to play later in development, in the establishment of the left-right (L/R) body axis. All vertebrates have characteristic and conserved L/R visceral asymmetries, for example the left-sided heart. Until recently very little was known about how the embryonic LR axis is established. In a recent study we showed that the chick homolog of nodal (Cnr-1 ) is expressed asymmetrically along the L/R axis before the appearance of normal morphological L/R asymmetry. In embryos in which Cnr-1 expression was experimentally altered so that it was symmetric along the LR axis or absent altogether, the early looping of the developing heart, normally to the right side, became random. This suggested the potential importance of Cnr-1 LR asymmetry for subsequent visceral morphogenesis. We have now shown that mouse nodal is also asymmetrically expressed in mouse embryos at similar stages and locations, as is Xenopus nodal related-1 (Xnr-1) in frog embryos. We also examined nodal expression in two mouse mutations which perturb L/R development, situs inversus viscerum (iv) and inversion of turning (inv). In both, nodal expression is strikingly affected, being reversed or converted to symmetry. These results further support a key role for nodal and nodal related genes in interpreting and relaying LR patterning information in vertebrates. This is also the first direct evidence that iv and inv function well before the appearance of morphological LR asymmetry during normal development.
| Lowe, L A; Yamada, S; Kuehn, M R (2001) Genetic dissection of nodal function in patterning the mouse embryo. Development 128:1831-43 |
| Pfendler, K C; Yoon, J; Taborn, G U et al. (2000) Nodal and bone morphogenetic protein 5 interact in murine mesoderm formation and implantation. Genesis 28:14-Jan |
| Fujinaga, M; Lowe, L A; Kuehn, M R (2000) alpha(1)-Adrenergic stimulation perturbs the left-right asymmetric expression pattern of nodal during rat embryogenesis. Teratology 62:317-24 |
| Lowe, L A; Yamada, S; Kuehn, M R (2000) HoxB6-Cre transgenic mice express Cre recombinase in extra-embryonic mesoderm, in lateral plate and limb mesoderm and at the midbrain/hindbrain junction. Genesis 26:118-20 |
| Campione, M; Steinbeisser, H; Schweickert, A et al. (1999) The homeobox gene Pitx2: mediator of asymmetric left-right signaling in vertebrate heart and gut looping. Development 126:1225-34 |
