Minimal model for emergent spatiotemporal patterning of synthetic Notch expression in vivo

Contact-mediated cell-cell communication can coordinate and pattern the growth of developing multicellular tissues and other cell collectives. Synthetic forms of this communication have the advantage of generating customizable signals which have the potential to shape 3D tissues for regenerative medicine and tissue engineering. However, the mechanisms that regulate the dynamics of a activated synthetic signal in a growing tissue is not well understood. Towards this goal, we present a vertex-based model of spatio-temporal synthetic Notch (synNotch) activation in the epithelium of the Drosophila wing imaginal disc. Through a combination of experiments and modeling, we show that a minimal model assuming uniform cell growth and contact dependent synthetic Notch signaling can largely account for the pattern of signal output observed in clonal populations of synNotch receiving cells in vivo. Our analysis indicates that the extent of synNotch output is dependent on the number of synNotch cells, and the shape of the synNotch cell population. The model highlights growth and output synthesis and degradation rates as the most useful parameters in predicting the extent of synNotch activation within a tissue and also sets the ground-work for predicting outputs of more complex synthetic circuits in vivo.