Talking to your neighbors across scales: Long-distance Notch signaling during patterning

Abstract

Tissue patterning is a critical part of animal development. Here we review the role that length- and timescales play in shaping patterns during development, focusing on the mechanisms by which Notch-mediated lateral inhibition signaling generates periodic tissue patterns. Because Notch ligands and receptors are membrane bound, the signaling that underlies lateral inhibition depends on direct cell-cell contacts. Nevertheless, there are many biological examples where effective Notch signaling occurs over distances larger than adjacent cells. Here, we summarize the theoretical and experimental evidence for mechanisms that modify the scale of Notch-mediated lateral inhibition. We focus on how cell protrusions, in addition to other cell behaviors like proliferation and neighbor exchange, allow for Notch signaling to both extend lateral inhibition beyond nearest neighbors and impact the timescale of patterning. Using recent examples, we examine how dynamic cell behaviors like the formation of protrusions affect the timing of Notch-mediated lateral inhibition as well as the density of the final tissue pattern. We suggest that mechanisms that affect the length and timescale of Notch signaling may have key implications for the evolution of patterns. This review highlights the role of cell behaviors in controlling the temporal and spatial dynamics of pattern formation across scales.