MUTATION OF AN AXONEMAL DYNEIN AFFECTS LEFT-RIGHT ASYMMETRY IN INVERSUS VISCERUM MICE

The development of characteristic visceral asymmetries along the left- right (LR) axis in an initially bilaterally symmetrical embryo is an e ssential feature of vertebrate patterning. The allelic mouse mutations inversus viscerum (iv)(1,2) and legless (lgl)(3,4) produce LR inversi on, or situs inversus, in half of live-born homozygotes, This suggests that the iv gene product drives correct LR determination, and in its absence this process is randomized(2), These mutations provide tools f or studying the development of LR-handed asymmetry and provide mouse m odels of human lateralization defects. At the molecular level, the nor mally LR asymmetric expression patterns of nodal(5) and lefty(6) are r andomized in iv/iv embryos, suggesting that iv functions early in the genetic hierarchy of LR specification, Here we report the positional c loning of an axonemal dynein heavy-chain gene, left/right-dynein (lrd) , that is mutated in both lgl and iv, lrd is expressed in the node of the embryo at embryonic day 7.5, consistent with its having a role in LR development(7). Our findings indicate that dynein, a microtubule-ba sed motor, is involved in the determination of LR-handed asymmetry and provide insight into the early molecular mechanisms of this process.