Avian models and the study of invariant asymmetry: how the chicken and the egg taught us to tell right from left.

While the external vertebrate body plan appears bilaterally symmetrical with respect to anterior-posterior and dorsal-ventral axes, the internal organs are arranged with a striking and invariant left-right asymmetry. This laterality is important for normal body function, as alterations manifest as numerous human birth defect syndromes. The left-right axis is set up very early during embryogenesis by an initial and still poorly understood break in bilateral symmetry, followed by a cascade of molecular events that was discovered 20 years ago in the chick embryo model. This gene regulatory network leads to activation of the pitx2 gene on the left side of the embryo which ultimately establishes asymmetric organogenesis of the heart, gut, brain, and other organs. In this review, we highlight the crucial contributions of the avian model to the discovery of the differential transcriptional cascades operating on the Left and Right sides, as well as to the physiological events operating upstream of asymmetric gene expression. The chick was not only instrumental in the discovery of mechanisms behind left-right patterning, but stands poised to facilitate inroads into the most fundamental aspects that link asymmetry to the rest of evolutionary developmental biology.