An important question in developmental biology is how vertebrate embryos acquire left-right asymmetry. Recent work has shown that in early embryos two TGF family members, nodal and lefty, are expressed in the left but not right lateral plate mesoderm, proceeding the asymmetry in the developing heart tube. Mutations in mice resulting in abnormal left-right asymmetry include iv (inversus viscerum) and lgl (legless), both which randomize left-right asymmetry. As iv functions upstream of nodal and lefty, it is likel to function very early in development. The PI has used positional cloning to clone the iv gene, and has identified it as an axonemal dynein heavy chain, named left/right dynein (lrd). This dynein heavy chain displays a mis-sense mutation in iv, and it is deleted in lgl.
The specific aims are designed to test the role of lrd in left/right asymmetry.
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