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Development. 2017 Apr 1;144(7):1177-1186. doi: 10.1242/dev.137950. Epub 2017 Feb 7.

Diversity of fate outcomes in cell pairs under lateral inhibition.

Author information

1
Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona Biomedical Research Park (PRBB), Dr Aiguader 88, Barcelona 08003, Spain.
2
Instituto de Física de Líquidos y Sistemas Biológicos (IFLYSIB), CONICET CCT-La Plata and Universidad Nacional de La Plata, Calle 59-789, La Plata 1900, Argentina.
3
Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona Biomedical Research Park (PRBB), Dr Aiguader 88, Barcelona 08003, Spain denavascuesj@cardiff.ac.uk jordi.g.ojalvo@upf.edu.
4
European Cancer Stem Cell Research Institute, School of Biosciences, Cardiff University, Hadyn Ellis Building, Maindy Road, Cardiff CF24 4HQ, UK denavascuesj@cardiff.ac.uk jordi.g.ojalvo@upf.edu.

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, the fate of which 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 contact areas, which affects the effective signalling threshold of individual cells. 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.

KEYWORDS:

Intestinal stem cells; Lateral inhibition; Neutral competition; Notch-Delta signalling; Symmetric cell division

PMID:
28174242
DOI:
10.1242/dev.137950
[Indexed for MEDLINE]
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