Engineered patterns of Notch ligands Jag1 and Dll4 elicit differential spatial control of endothelial sprouting
Laura A. Tiemeijer, Tommaso Ristori, Oscar M. J. A. Stassen, Jaakko J. Ahlberg, Jonne J.J. de Bijl, Christopher S. Chen, Katie Bentley, Carlijn V. C. Bouten, Cecilia Sahlgren
Abstract
models to analyze the ability of micropatterned Jag1 and Dll4 ligands to spatially control endothelial sprouting. Dll4 patterns, but not Jag1 patterns, elicited spatial control. Computational simulations of the underlying signaling dynamics suggest that different timing of Notch activation by Jag1 and Dll4 underlie their distinct ability to spatially control sprouting. Hence, Dll4 patterns efficiently direct the sprouts, whereas longer exposure to Jag1 patterns is required to achieve spatial control. These insights in sprouting regulation offer therapeutic handles for spatial regulation of angiogenesis.