CONSERVED LEFT-RIGHT ASYMMETRY OF NODAL EXPRESSION AND ALTERATIONS INMURINE SITUS-INVERSUS

VERTEBRATES have characteristic and conserved left-right (L-R) viscera l asymmetries, for example the left-sided heart. In humans, alteration s 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 molec ular asymmetry might be important for subsequent visceral morphogenesi s(2). Here we show that nodal(3) is asymmetrically expressed in mice a t similar stages, as is Xnr-1 (for Xenopus nodal related-1)(4) in frog s. We also examine nodal expression in two mouse mutations that pertur b L-R development, namely situs inversus viscerum (iv)(5), in which as signment of L-R asymmetry is apparently random and individuals develop either normally or are mirror-image-reverse (situs inversus), and inv ersion 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 suppo rt a key role for nodal and nodal-related genes in interpreting and re laying L-R patterning information in vertebrates. To our knowledge, ou r results provide the first direct evidence that iv and inv normally f unction well before the appearance of morphological L-R asymmetry.