Understanding the Principles of Pattern Formation Driven by Notch Signaling by Integrating Experiments and Theoretical Models

Bocci, FedericoOnuchic, José NelsonJolly, Mohit Kumar2020-11-032020-11-032020Bocci, Federico, Onuchic, José Nelson and Jolly, Mohit Kumar. "Understanding the Principles of Pattern Formation Driven by Notch Signaling by Integrating Experiments and Theoretical Models." <i>Frontiers in Physiology,</i> 11, (2020) Frontiers: https://doi.org/10.3389/fphys.2020.00929.https://hdl.handle.net/1911/109482Notch signaling is an evolutionary conserved cell-cell communication pathway. Besides regulating cell-fate decisions at an individual cell level, Notch signaling coordinates the emergent spatiotemporal patterning in a tissue through ligand-receptor interactions among transmembrane molecules of neighboring cells, as seen in embryonic development, angiogenesis, or wound healing. Due to its ubiquitous nature, Notch signaling is also implicated in several aspects of cancer progression, including tumor angiogenesis, stemness of cancer cells and cellular invasion. Here, we review experimental and computational models that help understand the operating principles of cell patterning driven by Notch signaling. First, we discuss the basic mechanisms of spatial patterning via canonical lateral inhibition and lateral induction mechanisms, including examples from angiogenesis, inner ear development and cancer metastasis. Next, we analyze additional layers of complexity in the Notch pathway, including the effect of varying cell sizes and shapes, ligand-receptor binding within the same cell, variable binding affinity of different ligand/receptor subtypes, and filopodia. Finally, we discuss some recent evidence of mechanosensitivity in the Notch pathway in driving collective epithelial cell migration and cardiovascular morphogenesis.engThis is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Understanding the Principles of Pattern Formation Driven by Notch Signaling by Integrating Experiments and Theoretical ModelsJournal articlehttps://doi.org/10.3389/fphys.2020.00929