Controlando a sinalização periódica de longo alcance para conduzir uma transição morfogenética: mero acaso, fortuita necessidade ou design inteligente?

quinta-feira, março 23, 2023

Controlling periodic long-range signalling to drive a morphogenetic transition

Hugh Z Ford, Angelika Manhart, Jonathan R Chubb 

Laboratory for Molecular Cell Biology and Department of Cell and Developmental Biology, University College London, United Kingdom; Department of Mathematics, University College London, United Kingdom; Faculty of Mathematics, University of Vienna, Austria

Mar 1, 2023 

Image/Imagem: Spiral tip circulation and spiral wave progression.


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.

Editor's evaluation

This fundamental work substantially advances our understanding of how multicellular structures transmit information over long ranges. Compelling approaches combining experiments and theory unravel the mechanism by which amoeba form migrating cellular waves by chemotaxis. The work will be of broad interest to cell and developmental biologists.