Cell-Cell Contact Area Affects Notch Signaling and Notch-Dependent Patterning

Oren Shaya, Udi Binshtok, Micha Hersch, Dmitri Rivkin, Sheila Weinreb, Liat Amir-Zilberstein, Bassma Khamaisi, Olya Oppenheim, Ravi A. Desai, Richard J. Goodyear, Guy P. Richardson, Christopher S. Chen, David Sprinzak*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

120 Scopus citations

Abstract

During development, cells undergo dramatic changes in their morphology. By affecting contact geometry, these morphological changes could influence cellular communication. However, it has remained unclear whether and how signaling depends on contact geometry. This question is particularly relevant for Notch signaling, which coordinates neighboring cell fates through direct cell-cell signaling. Using micropatterning with a receptor trans-endocytosis assay, we show that signaling between pairs of cells correlates with their contact area. This relationship extends across contact diameters ranging from micrometers to tens of micrometers. Mathematical modeling predicts that dependence of signaling on contact area can bias cellular differentiation in Notch-mediated lateral inhibition processes, such that smaller cells are more likely to differentiate into signal-producing cells. Consistent with this prediction, analysis of developing chick inner ear revealed that ligand-producing hair cell precursors have smaller apical footprints than non-hair cells. Together, these results highlight the influence of cell morphology on fate determination processes.

Original languageEnglish
Pages (from-to)505-511.e6
JournalDevelopmental Cell
Volume40
Issue number5
DOIs
StatePublished - 13 Mar 2017

Funding

FundersFunder number
Boris Shraiman
Israeli Science Foundation1021/11
National Institute of Biomedical Imaging and BioengineeringR01EB000262
National Institute of Biomedical Imaging and Bioengineering
Wellcome Trust087377
Wellcome Trust
European Research Council682161
European Research Council

    Keywords

    • Notch signaling
    • cell morphology
    • cell-cell contact
    • inner ear
    • lateral inhibition
    • live cell imaging

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