title: Cell-Cell Contact Area Affects Notch Signaling and Notch-Dependent Patterning.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Wise Faculty of Life Science, Tel Aviv University, Tel Aviv, 69978, Israel.
authors.forename: Oren
authors.initials: O
authors.lastname: Shaya
authors.affiliation: Department of Biochemistry and Molecular Biology, Wise Faculty of Life Science, Tel Aviv University, Tel Aviv, 69978, Israel.
authors.forename: Udi
authors.initials: U
authors.lastname: Binshtok
authors.affiliation: Department of Medical Genetics, University of Lausanne, Lausanne 1015, Switzerland; Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland.
authors.forename: Micha
authors.initials: M
authors.lastname: Hersch
authors.affiliation: Department of Biochemistry and Molecular Biology, Wise Faculty of Life Science, Tel Aviv University, Tel Aviv, 69978, Israel.
authors.forename: Dmitri
authors.initials: D
authors.lastname: Rivkin
authors.affiliation: Department of Biochemistry and Molecular Biology, Wise Faculty of Life Science, Tel Aviv University, Tel Aviv, 69978, Israel.
authors.forename: Sheila
authors.initials: S
authors.lastname: Weinreb
authors.affiliation: Department of Biochemistry and Molecular Biology, Wise Faculty of Life Science, Tel Aviv University, Tel Aviv, 69978, Israel.
authors.forename: Liat
authors.initials: L
authors.lastname: Amir-Zilberstein
authors.affiliation: Department of Biochemistry and Molecular Biology, Wise Faculty of Life Science, Tel Aviv University, Tel Aviv, 69978, Israel.
authors.forename: Bassma
authors.initials: B
authors.lastname: Khamaisi
authors.affiliation: Department of Biochemistry and Molecular Biology, Wise Faculty of Life Science, Tel Aviv University, Tel Aviv, 69978, Israel.
authors.forename: Olya
authors.initials: O
authors.lastname: Oppenheim
authors.affiliation: University College London, Department of Cell and Developmental Biology and Institute for Physics of Living Systems, London WC1E 6BT, UK; The Francis Crick Institute, London NW1 1AT, UK.
authors.forename: Ravi A
authors.initials: RA
authors.lastname: Desai
authors.affiliation: Sussex Neuroscience, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QG, UK.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Goodyear
authors.affiliation: Sussex Neuroscience, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QG, UK.
authors.forename: Guy P
authors.initials: GP
authors.lastname: Richardson
authors.affiliation: The Biological Design Center and Biomedical Engineering, Boston University, Boston, MA 02215, USA; The Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, Wise Faculty of Life Science, Tel Aviv University, Tel Aviv, 69978, Israel. Electronic address: davidsp@post.tau.ac.il.
authors.forename: David
authors.initials: D
authors.lastname: Sprinzak
mesh_terms: D000818:Animals; D019521:Body Patterning; D016466:CHO Cells; D002450:Cell Communication; D002645:Chickens; D006224:Cricetinae; D003412:Cricetulus; D004285:Dogs; D004705:Endocytosis; D005260:Female; D006801:Humans; D061985:Madin Darby Canine Kidney Cells; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D051880:Receptors, Notch
keywords: Notch signaling; cell morphology; cell-cell contact; inner ear; lateral inhibition; live cell imaging