A Multi-cell, Multi-scale Model of Vertebrate Segmentation and Somite Formation
(A) Our biological submodel of the clock-wavefront readout network. Notch signaling regulates EphA4 through cMeso (Mesp2), cytoplasmic β-catenin in the Wnt3a pathway stabilizes N-CAM and N-cadherin at the plasma membrane, and functional ephrinB2 signaling requires Paraxis, downstream of Wnt3a signaling. When FGF8 signaling decreases below a threshold, it releases the inhibition of cMeso, Paraxis and N-Cam/N-cadherin, leading to expression of adhesion proteins on the cell membrane. (B) A schematic of the Boolean cell-type determination network submodel implemented in our computational model. The computational submodel is a simplified implementation of the biological submodel in (A). In our current computational model, k1 = 21.28 and k2 = 0.406 nM. (C) Time series of Lfng, β-catenin and Axin2 oscillations in a simulated PSM cell at the determination-front concentrations of FGF8 and Wnt3a ([FGF8] = 13.9 nM, [Wnt3a] = 0.55 nM). When the external FGF8 concentration falls below the determination threshold, the relative and absolute concentrations of Lfng, β-catenin and Axin2 determine the fate of the cell in our computational model according to the determination submodel in (B). For more information see INTRODUCTION: Clock-wavefront read-out model and METHODS: Clock-wavefront model.