Cell-cell contact area affects Notch signaling and Notch-dependent patterning

Shaya, Oren, Binshtok, Udi, Hersh, Micha, Rivken, Dmitri, Weinreb, Sheila, Amir-Siberstein, Liat, Khamaisi, Bassma, Oppenheim, Olya, Desai, Ravi A, Goodyear, Richard J, Richardson, Guy P, Cheng, Christopher S and Sprinzak, David (2017) Cell-cell contact area affects Notch signaling and Notch-dependent patterning. Developmental Cell, 40 (5). pp. 505-511. ISSN 1534-5807

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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 microns to tens of microns. 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.

Item Type: Article
Keywords: Notch signaling; lateral inhibition; cell morphology; live cell imaging; cell-cell contact; inner ear
Schools and Departments: School of Life Sciences > Neuroscience
Research Centres and Groups: Sussex Neuroscience
Depositing User: Guy Richardson
Date Deposited: 19 Dec 2017 15:10
Last Modified: 02 Jul 2019 16:18
URI: http://sro.sussex.ac.uk/id/eprint/71789

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Project NameSussex Project NumberFunderFunder Ref
The Tectorial Membrane and the Sensory Hair Bundles of the Inner Ear: Mechanisms of Development and Effects of Deafness-Causing MutationsG0162WELLCOME TRUST087737