Development of the left-right axis.

Left-right is not an axis in the conventional sense but rather two mirror-image proximodistal axes, upon which a quantal piece of positional information (leftness or rightness) is superimposed for laterally asymmetric organ development. We are attempting to establish the stages at which left-right is specified and determined, but this is complicated by the apparent loss of normal handed development in embryos that are cultured from pre-neural plate stages. Experiments suggest that left-right is determined by the first somite stage. The loss of normal left-right development in early cultures is probably not due to removal of some maternal signal, even though embryos do develop in vivo with their axes in a specific orientation relative to the uterus. The fact that there are two random embryonic axis orientations, 180 degrees opposed to one another, and that the axes of the two uterine horns are mirror-images of each other make it unlikely that the uterus could impart a sense of left-right to the embryo. The right ovary produces more eggs than the left one; this is reversed in iv/iv situs inversus mice. Analysis of iv/iv mice shows a correlation of left-right abnormalities with sex and close relationships between the abnormal left-right development of some organs, for example the heart and spleen, that have no obvious developmental connection.