Controlling periodic long-range signalling to drive a morphogenetic transition

Abstract
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Abstract

Cells use signal relay to transmit information across tissue scales. However, the production of information carried by signal relay remains poorly characterised. To determine how the coding features of signal relay are generated, we used the classic system for long-range signalling: the periodic cAMP waves that drive Dictyostelium collective migration. Combining imaging and optogenetic perturbation of cell signalling states, we find that migration is triggered by an increase in wave frequency generated at the signalling centre. Wave frequency is regulated by cAMP wave circulation, which organises the long-range signal. To determine the mechanisms modulating wave circulation, we combined mathematical modelling, the general theory of excitable media and mechanical perturbations to test competing models. Models in which cell density and spatial patterning modulate the wave frequency cannot explain the temporal evolution of signalling waves. Instead, our evidence leads to a model where wave circulation increases the ability for cells to relay the signal, causing further increase in the circulation rate. This positive feedback between cell state and signalling pattern regulates the long-range signal coding that drives morphogenesis.

Data availability

The high resolution movies of cAMP signalling and optogenetic treatments can be accessed at UCL's institutional repository using the DOI: 10.5522/04/21360975. All image analysis and mathematical modelling methodology described in full in methods section. Matlab code for the agent-based model is provided.

The following data sets were generated

1. Chubb J
2. Ford H
(2022) cAMP signalling movies and optogenetics
DOI: 10.5522/04/21360975.

https://doi.org/10.5522/04/21360975.v1

Article and author information

Author details

Hugh Z Ford

Laboratory for Molecular Cell Biology, University College London, London, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Angelika Manhart

Department of Mathematics, University College London, London, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Jonathan R Chubb

Laboratory for Molecular Cell Biology, University College London, London, United Kingdom

For correspondence
j.chubb@ucl.ac.uk

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-6898-9765

Funding

Wellcome Trust (202867/Z/16/Z)

Jonathan R Chubb

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.