Figure 1. In normal conditions (situs solitus) (a), the right lung has three lobes, whereas the left lung has two. In addition, the apex of the heart points to the left side, the liver is on the right side and the stomach and spleen are on the left side. Although not shown in the figure, the gut coils counterclockwise in the abdominal cavity. In the condition known as right isomerism (b), also called asplenia syndrome, the heart and lungs are double-right (as indicated by the structure of the heart chambers and by both lungs having three lobes), as is the liver, which is generally found in a midline position. The stomach may be located on either side or in the midline, and the spleen is absent. In left isomerism (c), also called polysplenia syndrome, the heart and lungs are double-left, the liver may be double-left, located in a midline position, or normal, and the stomach is usually found in a midline position. There is always more than one spleen (termed splenules), although multilobulated single spleens may also occur. Situs inversus refers to the complete mirror-image reversal of organ asymmetry (d). Since laterality defects are highly variable, the figure depicts simplified cases, and is not intended to accurately portray the whole range of possible defects. The terms situs inversus and right or left isomerism can also be used to describe laterality defects in individual organs, even if they are not included in specific syndromes. (Figure adapted from Capdevila et al., 2000)

Figure 2. In the early mouse embryo, it is postulated that a leftward nodal flow (indicated by the arrows) activates left-specific gene expression, represented by asymmetric expression of Nodal in and around the node. Several components of the molecular motors in the cilia have been shown to be necessary for this initial breaking of symmetry (Lrd, KIF-3A, KIF-3B). The product of the inv gene is also necessary for this step, although its exact function is still unclear. The transfer of asymmetric information from the node to the lateral plate mesoderm (LPM) is carried out in the chick by means of the protein Caronte (Car). Car protein on the left side antagonizes the repression of nodal transcription by bone morphogenic proteins (BMPs). In turn, Nodal represses SnR, which is itself a repressor of Pitx2, so that SnR is expressed on the right and Pitx2 on the left LPM. At the midline, the Lefty-1 protein might act as a barrier, thus preventing ectopic expression of left-specific genes in the right side of the embryo. (Model adapted from Capdevila et al.,)(2000)