Fig. 1.

Summarized schematic of left-right (LR) asymmetry cascades in the mouse embryo. The node is viewed from the dorsal side. Early symmetry breaking signals such as asymmetric ion transporter activities in Xenopus, chick, zebrafish, and possibly other vertebrates are transmitted to the node through unknown mechanisms. Notch signaling directly induces perinodal expression of Nodal (red), a TGF-β family ligand, which is necessary for expression of Nodal in the left lateral plate mesoderm (LPM). Simultaneously, the leftward nodal flow leads to the accumulation of intracellular Ca²⁺ that is presumably required for LR asymmetric establishment. The Nodal in the LPM up-regulates its own expression in a positive feedback loop and induces expression of Lefty2 (dark blue) and Pitx2 (yellow) in the LPM, and expression of Lefty1 (light blue) in the left prospective floor plate, dorsal to the notochord. By antagonizing the activity of Nodal, Lefty1 limits the range of Nodal activity and Lefty2 inhibits the spread of Nodal signal from the left side to the right side. The Pitx2 maintains left-specific signals during organ morphogenesis. A anterior, P posterior, R right, L left