Fig. 5. Sequential function of Nodal signaling in left-right patterning in the mouse embryo. (A) Following initial symmetry breaking around the node, possibly as a consequence of ciliary-based nodal flow, Nodal (green arrow) and/or Gdf1 signals become elevated on the left side of the node, and are antagonized by Cer2 (red). Nodal pathway activity then propagates to the left lateral plate mesoderm to activate left-sided Nodal expression, most likely through direct long-range action. (B) Nodal auto-regulates its own expression, which spreads through the left lateral plate mesoderm (green) through a positive-feedback loop. Lefty2 is induced through a negative-feedback loop, and subsequently downregulates Nodal expression (red bar). Axial midline expression of Lefty1 prevents the spread of left-sided Nodal signals, and suppresses ectopic Nodal activation on the right side.