Specification of Left-Right Asymmetry
There has been considerable progress in understanding how restricted patterns of gene expression and differentiation are set up along the anteriorposterior (A-P) and dorsal-ventral (D-V) axes of the vertebrate embryo, and how these provide the fundamental framework for regionalized visceral, neural and cardiovascular organogenesis. Intimately linked, and in many ways equally important, is the morphogenesis that occurs orthogonal to these axes and leads to the left-right (L-R) asymmetric body plan. This plan is evident in all vertebrates as a stereotypical looping of the heart, gut, and the positioning of associated organs. In humans, complete inversion of the normal L-R body plan, called situs inversus, is not deleterious to health, but situations in which some tissues adopt the normal orientation while others are inverted (heterotaxia or situs ambiguus), have profound medical consequences, such as improper connections of the large blood vessels and abnormally chambered hearts (see Kathiriya and Srivastava 2000). Up to 1 in 8500 of human births have congenital defects associated with laterality defects, but there are likely to be many more losses that are unaccounted for in utero. Although the L-R asymmetry program appears to be quite sensitive to a variety of environmental and genetic disturbances, the overall uniformity of L-R patterning both within and between vertebrate species implies a strong, and to some degree conserved, underlying genetic regulation.
KeywordsSitus Inversus Nodal Signaling Zebra Fish Pineal Organ Heart Tube
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