Fig. 5. Genetic pathway for, and signal transfer during, left-right (LR) patterning. (A) A genetic pathway for LR patterning. Only major components are shown. An asymmetric signal generated in the node initiates Nodal-Lefty1-Lefty2 regulatory loops in the left lateral plate mesoderm (LPM). Nodal activity induces Pitx2 expression in the left LPM. The broken line represents the midline. Lrd and Inv are required to generate asymmetric signal in the node. Foxh1 is a component of the Nodal-Lefty loops. (B) Signal transfer during LR patterning. A ventral view of an E8.0 mouse embryo. At least four steps of signal transfer take place during LR patterning: (1) from the node to the left LPM; (2) within the LPM; (3) from the left and right LPM to the midline; and (4) from the midline to the LPM. The Nodal signal is transferred in the second and third steps, but the identity of the signal that is transferred from the node to the LPM is unknown. In the fourth step, a midline signal (Lefty1) negatively regulates Nodal in the LPM. Pink arrow, the nodal flow; pink oval, a small region of LPM that initially receives the signal from the node. The expression domains of Nodal (red), and Lefty1 and Lefty2 (blue) are indicated.