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

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posted on 2023-06-09, 09:10 authored by Oren Shaya, Udi Binshtok, Micha Hersh, Dmitri Rivken, Sheila Weinreb, Liat Amir-Siberstein, Bassma Khamaisi, Olya Oppenheim, Ravi A Desai, Richard GoodyearRichard Goodyear, Guy Richardson, Christopher S Cheng, David Sprinzak
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.

Funding

The Tectorial Membrane and the Sensory Hair Bundles of the Inner Ear: Mechanisms of Development and Effects of Deafness-Causing Mutations; G0162; WELLCOME TRUST; 087737

History

Publication status

  • Published

File Version

  • Accepted version

Journal

Developmental Cell

ISSN

1534-5807

Publisher

Elsevier

Issue

5

Volume

40

Page range

505-511

Department affiliated with

  • Neuroscience Publications

Research groups affiliated with

  • Sussex Neuroscience Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2017-12-19

First Open Access (FOA) Date

2018-03-13

First Compliant Deposit (FCD) Date

2017-12-06

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