Abstract
Tissue organization and patterning are critical during development when genetically identical cells take on different fates. Lateral signalling plays an important role in this process by helping to generate self-organized spatial patterns in an otherwise uniform collection of cells. Recent data suggest that lateral signalling can be mediated both by junctional contacts between neighbouring cells and via cellular protrusions that allow non-neighbouring cells to interact with one another at a distance. However, it remains unclear precisely how signalling mediated by these distinct types of cell–cell contact can physically contribute to the generation of complex patterns without the assistance of diffusible morphogens or pre-patterns. To explore this question, in this work we develop a model of lateral signalling based on a single receptor/ligand pair as exemplified by Notch and Delta. We show that allowing the signalling kinetics to differ at junctional versus protrusion-mediated contacts, an assumption inspired by recent data which show that the cleavage of Notch in several systems requires both Delta binding and the application of mechanical force, permits individual cells to act to promote both lateral activation and lateral inhibition. Strikingly, under this model, in which Delta can sequester Notch, a variety of patterns resembling those typical of reaction–diffusion systems is observed, together with more unusual patterns that arise when we consider changes in signalling kinetics, and in the length and distribution of protrusions. Importantly, these patterns are self-organizing—so that local interactions drive tissue-scale patterning. Together, these data show that protrusions can, in principle, generate different types of patterns in addition to contributing to long-range signalling and to pattern refinement.
Highlights
Patterning is key to the development of complex multicellular organisms
How can initially uniform tissues self-organize into complex spatial patterns without a chemical pre-pattern or the ability of cells to migrate? In this work, we propose that a lateral inhibition mechanism comprised a single ligand–receptor pair based on Notch–Delta signalling can generate a wide set of patterns
These vary from regularly spaced dots and clusters to stripes, radii, labyrinths and more—extending the set previous described for typical Notch –Delta models of lateral inhibition
Summary
Patterning is key to the development of complex multicellular organisms. the organization of initially uniform cells into regular motifs such as stripes or spots has been widely documented across species and scales. Spot patterns of varying density and regularity can be obtained by modulating the protrusion dynamics and length [1], it is not clear whether, in the absence of molecular diffusion, more complex patterns can emerge To test this idea, here we develop a model of lateral inhibition with feedback based on Notch –Delta signalling to explore the capacity of contact-mediated signalling to generate diverse patterns. This type of juxtacrine signalling leads to a variety of self-organizing patterns, ranging from sparsely or densely spaced stripes, labyrinths and radii, to clusters and regular salt-and-pepper patterns of different density. We explore the role of the signalling dynamics, protrusion length and directionality in the patterning process and consider its broader implications for our understanding of developmental patterning
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