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Modeling the Notch Response

  • Udi Binshtok
  • David Sprinzak
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1066)

Abstract

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.

Keywords

NOTCH signaling Mathematical modeling Pattern formation Lateral inhibition Boundary formation Cis-inhibition Cell morphology Cell division Filopodia 

Abbreviations

SOP

Sensory organ precursors

NICD

NOTCH intra-cellular domain

Dll1

DELTA-LIKE-1

Dll4

DELTA-LIKE-4

EGF

Epidermal growth factor

VEGF

Vascular endothelial growth factor

VEGFr

Vascular endothelial growth factor receptor

ISCs

Intestinal stem cells

EBs

Enteroblasts

PSM

Presomitic Mesoderm

Notes

Acknowledgments

This manuscript was supported by a grant from the European Research Council (grant no. 682161).

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Biochemistry and Molecular Biology, George S. Wise Faculty of Life ScienceTel Aviv UniversityTel AvivIsrael

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