Ectopic expression of sonic hedgehog leads to symmetrical nodal expression and randomization of heart looping. (A) Wild-type expression of the chick nodal gene, showing expression on the left side (dark area). Nearly all hearts develop right-sided loops. This pattern is also seen when pellets containing control substances are implanted into the right side of Hensen's node, or when a Sonic hedgehog-containing pellet is implanted on the left side (where sonic hedgehog is usually expressed). (B) When a Sonic hedgehog pellet is implanted on the right side of the node, the expression of nodal becomes bilaterally symmetrical. (From Levin et al. 1995; photographs courtesy of the authors.)