Vertebrate left-right asymmetry: old studies and new insights.

During vertebrate embryonic development, the organs of the chest and abdomen, heart, lung and gastrointestinal tract, acquire characteristic asymmetric positions with respect to the left-right body axis. In the beginning of the 20th century Hans Spemann and his co-workers described manipulations of amphibian embryos which resulted in inversion of organ laterality in a predictable manner. Hedwig Wilhelmi concluded from these experiments that determinants on the left side of the embryo specify laterality, and Meyer postulated that a mediator should transfer this positional information to the forming heart. In this review we discuss the classical experiments in the light of recent advances in the molecular understanding of left-right development, with a focus on the mediator role of the homeobox gene Pitx2.