Figure 4. Modeling of mouse digit patterning with realistic signaling networks.
(a) Experimental patterns of BMP (green), pSmad1/5/8 (purple), Sox9 (blue), and β-catenin (red) in a mouse limb at stage E11.5 (data reproduced from Raspopovic et al., 2014). (b) Extension of a previously proposed simple three-node network for digit patterning involving BMP, Sox9, and Wnt to a more realistic five-node network incorporating known interactions (black) between Wnt (W, red), BMP (B, green), Smad1/5/8 (Sm, pink), Sox9 (S, blue), and β-catenin (β, red); interactions predicted by RDNets are shown in gray, and dashed lines correspond to alternative interactions that implement networks with similar robustness. The simulations of the new five-node network recapitulate the unintuitive out-of-phase pattern between BMP expression (green) and its own signaling through pSmad1/5/8 (purple). The mathematical analysis predicts that these patterns can be formed when β-catenin inhibits Sox9 indirectly through pSmad1/5/8. See Appendix 6 for a full list of parameters.