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Diversity of fate outcomes in cell pairs under lateral inhibition

View ORCID ProfileNara Guisoni, View ORCID ProfileRosa Martinez-Corral, View ORCID ProfileJordi Garcia Ojalvo, View ORCID ProfileJoaquín de Navascués
doi: https://doi.org/10.1101/032078
Nara Guisoni
1Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona Biomedical Research Park (PRBB), Dr. Aiguader 88, 08003 Barcelona, Spain.
2Instituto de Física de Líquidos y Sistemas Biológicos, CONICET & Universidad Nacional de La Plata, Calle 59-789, 1900 La Plata, Argentina.
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Rosa Martinez-Corral
1Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona Biomedical Research Park (PRBB), Dr. Aiguader 88, 08003 Barcelona, Spain.
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Jordi Garcia Ojalvo
1Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona Biomedical Research Park (PRBB), Dr. Aiguader 88, 08003 Barcelona, Spain.
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  • For correspondence: denavascuesj@cardiff.ac.uk jordi.g.ojalvo@upf.edu
Joaquín de Navascués
3European Cancer Stem Cell Research Institute, School of Biosciences, Cardiff University, Hadyn Ellis Building, Maindy Road, Cardiff CF24 4HQ, UK.
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  • For correspondence: denavascuesj@cardiff.ac.uk jordi.g.ojalvo@upf.edu
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Abstract

Cell fate determination by lateral inhibition via Notch/Delta signalling has been extensively studied. Most formalised models consider Notch/Delta interactions in fields of cells, with parameters that typically lead to symmetry breaking of signalling states between neighbouring cells, commonly resulting in salt-and-pepper fate patterns. Here we consider the case of signalling between isolated cell pairs, and find that the bifurcation properties of a standard mathematical model of lateral inhibition can lead to stable symmetric signalling states. We apply this model to the adult intestinal stem cell (ISC) of Drosophila, whose fate is stochastic but dependent on the Notch/Delta pathway. We observe a correlation between signalling state in cell pairs and their contact area. We interpret this behaviour in terms of the properties of our model in the presence of population variability in signalling thresholds. Our results suggest that the dynamics of Notch/Delta signalling can contribute to explain stochasticity in stem cell fate decisions, and that the standard model for lateral inhibition can account for a wider range of developmental outcomes than previously considered.

Summary statement Notch/Delta-mediated lateral inhibition in cell pairs can result in symmetric signalling depending on the activation threshold, which can modulate cell-fate decisions depending on contact area.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted March 22, 2016.
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Diversity of fate outcomes in cell pairs under lateral inhibition
Nara Guisoni, Rosa Martinez-Corral, Jordi Garcia Ojalvo, Joaquín de Navascués
bioRxiv 032078; doi: https://doi.org/10.1101/032078
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Diversity of fate outcomes in cell pairs under lateral inhibition
Nara Guisoni, Rosa Martinez-Corral, Jordi Garcia Ojalvo, Joaquín de Navascués
bioRxiv 032078; doi: https://doi.org/10.1101/032078

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