Nodal/Activin Signaling in ES Cell Fate Decisions Figure 8. Model of the Mechanism of ES Cell Fate Decisions Directed by Graded Nodal/Activin Signaling. Schema of the components and signal transduction of the Nodal/Activin pathway starting with different concentrations of ligands external to the ES cell lipid bilayer membrane and terminating with the pSmad2 transcriptional complex regulating Oct4 and different subsets of target genes in the nucleus. Red arrows show the signal transduction circuit, black arrows show transcription and translation of pSmad2 target genes while green inhibitory lines indicate negative feedback. Protein names in red are targets identified in the microarray analysis and/or pSmad2 ChIP-Seq. Color gradients from red to green denote components exhibiting a dose-dependent response from high (+) to low (–) activity. Plots represent the graded, high and low signaling dominant models of pSmad2 binding during differential signaling with the vertical axis showing the level of binding against the horizontal axis with increasing signaling levels from left to right. Different cell fate decisions and the events triggering them are indicated by lines and arrows in red to green color gradients. doi:10.1371/journal.pgen.1002130.g008 PLoS Genetics | www.plosgenetics.org 16 June 2011 | Volume 7 | Issue 6 | e1002130