During vertebrate embryonic development, the organs of the chest and abdome
n, heart, lung and gastrointestinal tract, aquire characteristic asymmetric
positions with respect to the left-right body axis. In the beginning of th
e 20th century Hans Spemann and his co-workers described manipulations of a
mphibian embryos which resulted in inversion of organ laterality in a predi
ctable manner. Hedwig Wilhelmi concluded from these experiments that determ
inants on the left side of the embryo specifiy laterality, and Meyer postul
ated that a mediator should transfer this positional information to the for
ming heart. In this review we discuss the classical experiments in the ligh
t of recent advances in the molecular understanding of left-right developme
nt, with a focus on the mediator role of the homeobox gene Pitx2.