Conserved and divergent mechanisms in left–right axis formation

Abstract

Vertebrates appear bilaterally symmetric but an internal left–right (L–R) axis is revealed by the placement of asymmetric organs about the midline. For example, the human heart is located to the left of the body cavity, whereas the liver is located to the right. Paired organs can also display L–R differences, as seen in human lungs, in which the right lung has three lobes and the left lung two. Alterations in L–R axis formation can lead to variations in the normal arrangement of organs, including complete inversion of the axis (situs inversus), randomized placement of organs (heterotaxia or situs ambiguus), and mirror image duplications of paired organs (isomerism). In the past 5 years important progress has been made in clarifying the embryological and molecular mechanisms underlying the development of laterality in different vertebrates. Surprisingly, however, it is still unclear if many of the strategies employed in one group of vertebrates are also applied in other groups. In this review, we compare the roles in L–R development ascribed to various molecules and embryological structures in the four common vertebrate model systems.