How cells communicate during tissue growth*

Cell-cell communication is essential during fundamental biological processes such as cell fate specification during morphogenesis. Synthetic forms of cell-cell communication through direct contact between neighboring cells can generate custom gene expression outputs, making them valuable for tissue engineering and regenerative medicine. As embryonic tissues are complex, active materials undergoing growth, we ask how the tissue growth process impacts synthetic cell-cell signal output. We will discuss experimental evidence, a computational model verified with experimental observations and hypothesized principles linking tissue growth driven changes in morphology and signal output patterns. Focusing on synthetic Notch (synNotch), a custom synthetic gene circuit, we discover that output forms a graded exponential spatial profile that extends several cell diameters from the signal source. Moreover, we show that the shape of the interface between signal sending and receiving cells is important in determining the output. Overall, we elucidate key biophysical principles that underlie complex emergent spatiotemporal patterns of cell-cell signaling output in growing tissues.