  Notch 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 to 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 such as the effects 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.
