The compulsion of chirality: toward an understanding of left–right asymmetry

Although it has long been clear that correct development of left–right (LR) asymmetry requires that tissues in the early embryo know whether they lie to the left or right of the midline, the molecular mechanisms that invariantly orient the LR axis have remained obscure. The recent demonstration that theiv (inverted viscerum) mutation in the mouse may be caused by a mutation in a gene encoding an axonemal dynein heavy chain has been much anticipated (Afzelius 1976; Brown et al. 1991; Levin and Nascone 1997) and sheds light on the earliest steps in the determination of LR asymmetry (Supp et al. 1997). However, many questions are also raised, such as what the roles of axonemal versus cytoplasmic dynein are, and how dynein action is transmitted across fields of cells, a prerequisite to the large-scale asymmetric gene expression known to be involved in determination of body asymmetry (Fujinaga 1996; Levin et al. 1997). In this review we discuss the nature of the information flow from molecular chirality to morphological and behavioral asymmetry as well as some possible molecular candidates for these processes. We also address the timing of initial LR decisions during embryogenesis, and evolutionary aspects of asymmetry.

Most internal organs in the chest and abdomen of all vertebrates lie asymmetrically along the LR body axis despite external bilateral symmetry of the organism itself. In all normal individuals, the LR axis is invariantly oriented such that the apex of the heart points to the left, the aorta loops to the right and the inferior vena cava runs to the left of the spinal column. Similarly, the right lung is divided into three lobes whereas the left has only two. Beneath the diaphragm, the stomach and spleen are on the left and the intestine runs from right to left. …