ABSTRACT
Humans and all other vertebrates externally appear, to be bilaterally symmetrical. The left and right arm are mirror images of each other, as are the legs and the left and right halves of the trunk. Underlying the external symmetry, however, is extensive left-right asymmetry of the internal organs. The thoracic organs, in particular, have a high degree of left-right asymmetry. The three basic body axes along which the vertebrate body plan is organized are anteroposterior (AP), dorsoventral (DV), and left-right (LR), and among these, the LR axis is unique in several ways. Left-right is the dependent axis, being determined by the previously established AP and DV axes. In addition, LR is a binary decision instead of a continuous gradient like the AP and DV axes. Finally, the handedness of left-right asymmetry is consistent across all vertebrates. This means that the organism not only needs to have a mechanism by which it creates asymmetry along the LR axis, but that there also has to be a mechanism that consistently aligns that asymmetry to the preexisting AP and DV axes. Why did the vertebrate organism evolve this additional level of spatial complexity? Perhaps it permitted the development of the more complex cardiopulmonary system that is necessary
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to support a larger organism dependent on active circulation instead of diffusion. This notion is supported by the high incidence of complex, often lethal cardiac defects in mice and humans with defective development of LR asymmetry. Study of genetic defects in left-right development in mice and humans have lead to significant insights into the molecular mechanism underlying this fascinating and unique step in vertebrate development.
