Conserved left-right asymmetry of nodal expression and alterations in murine situs inversus

VERTEBRATES have characteristic and conserved left-right (L-R) visceral asymmetries, for example the left-sided heart. In humans, alterations of L-R development can have serious clinical implications, including cardiac defects(1). Although little is known about how the embryonic L-R axis is established, a recent study in the chick embryo revealed L-R asymmetric expression of several previously cloned genes, including Cnr-1 (for chicken nodal-related-1), and indicated how this L-R molecular asymmetry might be important for subsequent visceral morphogenesis(2). Here we show that nodal(3) is asymmetrically expressed in mice at similar stages, as is Xnr-1 (for Xenopus nodal related-1)(4) in frogs. We also examine nodal expression in two mouse mutations that perturb L-R development, namely situs inversus viscerum (iv)(5), in which assignment of L-R asymmetry is apparently random and individuals develop either normally or are mirror-image-reverse (situs inversus), and inversion of embryonic turning (inv)(6), in which all individuals develop with situs inversus. 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 L-R patterning information in vertebrates. To our knowledge, our results provide the first direct evidence that iv and inv normally function well before the appearance of morphological L-R asymmetry.