Fig. 7. Proposed model of the regulation and function of chick Cer in the left-side mesoderm. At Hamburger and Hamilton stage 5-6 (HH5-6), the early expression of Nodal in the node is activated on the left side by Notch and Shh signaling pathways, and is repressed on the right side by Fgf8. At HH7, the Nodal protein released by the node directly activates chick Cer (cCer) and Nodal expression in the adjacent left paraxial and lateral plate mesoderm (P+LPM). Nodal signal is transduced into the phosphorylation of SMAD2 and/or SMAD3, which then bind SMAD4, translocate into the nucleus and synergize with the FoxH1 transcription factor in the activation of cCer transcription. At HH8, Nodal protein produced by the P+LPM cells upregulates cCer and Nodal expression throughout the left lateral plate mesoderm (broken arrows). cCer protein is then required to downregulate the Nodal signal in the left lateral plate mesoderm and prevent it from crossing to the right side of the chick embryo. L, left; R, right.