Molecular Mechanisms of Notch Signaling

Udi Binshtok, David Sprinzak, Binshtok, Udi, Sprinzak, David

NOTCH signaling regulates developmental processes in all tissues and all organisms across the animal kingdom. It is often involved in coordinating the differentiation of neighboring cells into different cell types. As our knowledge on the structural, molecular and cellular properties of the NOTCH pathway expands, there is a greater need for quantitative methodologies to get a better understanding of the processes controlled by NOTCH signaling. In recent years, theoretical and computational approaches to NOTCH signaling and NOTCH mediated patterning are gaining popularity. Mathematical models of NOTCH mediated patterning provide insight into complex and counterintuitive behaviors and can help generate predictions that can guide experiments. In this chapter, we review the recent advances in modeling NOTCH mediated patterning processes. We discuss new modeling approaches to lateral inhibition patterning that take into account cis-interactions between NOTCH receptors and ligands, signaling through long cellular protrusions, cell division processes, and coupling to external signals. We also describe models of somitogenesis, where NOTCH signaling is used for synchronizing cellular oscillations. We then discuss modeling approaches that consider the effect of cell morphology on NOTCH signaling and NOTCH mediated patterning. Finally, we consider models of boundary formation and how they are influenced by the combinatorial action of multiple ligands. Together, these topics cover the main advances in the field of modeling the NOTCH response.