(670e) Crosstalk Between Cell-Cell Contact and Soluble Factors In Regulating Epithelial Cell Proliferation

Multicellular patterns and structures emerge as cells execute instructions received from cues in their microenvironment. Deciphering how cells integrate these cues to achieve an organized, functional structure is a fundamental question in biology with important biomedical implications in areas such as tissue engineering and regenerative medicine. An essential element in multicellular assembly involves direct cell-cell interactions. Cell-cell contacts are not only physical links between neighboring cells, but also sources of biochemical signals that instruct cellular behavior. Our lab is investigating how direct cell-cell interactions crosstalk with other environmental cues to affect individual cell fate choices, and thereby, generate multicellular patterns. In this talk, I will describe recent results that reveal a coupling between epidermal growth factor (EGF) and cell-cell contact in regulating the proliferation of human epithelial cells. This coupling between a long-range signal (EGF) and short-range cell-cell interactions gives rise to transient spatial heterogeneity in cell cycle activity. Single-cell measurements show that specific signaling pathways are influenced by cell-cell contact only when EGF concentration is below a critical concentration. These results reveal that quantitative competition between EGF and contact signaling pathways gives rise to spatiotemporal dynamics of epithelial cell proliferation.