Fig. 7. Three-step model for BMP antagonism by noggin and chordin in promoting Nodal expression during left-right axis establishment in mouse. (A) Step 1, from presomitic to 1s. Nog and Chrd promote Nodal expression around the node. Leftward flow is created by cilia rotation. (B) Step 2, 2-3s. Nodal expression is higher on the left than right side of the node, but both left and right LPM receive some level of Nodal-dependent signals. Bilateral BMP signals in LPM repress Nodal signaling and its positive-feedback loop. Stronger Nodal signals to left LPM induce increased BMP antagonist expression. (C) Step 3, 4-5s. Increased Nog and Chrd expression in left LPM elevates left-side-specific BMP antagonism, inhibiting the repressive action of BMP on Nodal expression. As a result, a robust Nodal positive-feedback loop is established in left LPM.