A new mechanism for spatial pattern formation via lateral and protrusion-mediated lateral signalling.
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.
Centre for Mathematics, Physics, and Engineering in the Life Sciences and Experimental Biology, University College London, London WC1E 6BT, UK zena.hadjivasiliou@unige.ch.|Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, UK.
Zena
0000-0003-1174-1421
Z
Hadjivasiliou
MRC-Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK.|Institute of Physics of Living Systems, University College London, London WC1E 6BT, UK.
Ginger L
GL
Hunter
MRC-Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK.|Institute of Physics of Living Systems, University College London, London WC1E 6BT, UK.
Buzz
B
Baum
D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D021961:Cell Membrane Structures / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008954:Models, Biological; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051880:Receptors, Notch; C064045:delta protein
Delta; Notch; lateral inhibition; patterning; protrusion signalling