Generating active T1 transitions through mechanochemical feedback
Abstract
Convergence-extension in embryos is controlled by chemical and mechanical signalling. A key cellular process is the exchange of neighbours via T1 transitions. We propose and analyse a model with positive feedback between recruitment of myosin motors and mechanical tension in cell junctions. The model produces active T1 events, which act to elongate the tissue perpendicular to the main direction of tissue stress. Using an idealized tissue patch comprising several active cells embedded in a matrix of passive hexagonal cells we identified an optimal range of mechanical stresses to trigger an active T1 event. We show that directed stresses also generate tension chains in a realistic patch made entirely of active cells of random shapes, and leads to convergence-extension over a range of parameters. Our findings show that active intercalations can generate stress that activates T1 events in neighbouring cells resulting in tension dependent tissue reorganisation, in qualitative agreement with experiments on gastrulation in chick embryos.
Data availability
The current manuscript is primarily a computational study, so no data have been generated for this manuscript. Modelling code is publically (GNU public license v 2.0) available on GitHub at: https://github.com/sknepneklab/ActiveJunctionModelThe experimental data presented in Figure 8 and Figure 8 - figure supplement 1 has been generated as described in the methods section.
Article and author information
Author details
Funding
Biotechnology and Biological Sciences Research Council (BB/N009789/1)
- Rastko Sknepnek
- Manli Chuai
- Cornelis Weijer
Biotechnology and Biological Sciences Research Council (BB/N009150/1-2)
- Ilyas Djafer-Cherif
- Silke Henkes
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2023, Sknepnek et al.
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.
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Further reading
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- Neuroscience
- Physics of Living Systems
Recent experimental studies showed that electrically coupled neural networks like in mammalian inferior olive nucleus generate synchronized rhythmic activity by the subthreshold sinusoidal-like oscillations of the membrane voltage. Understanding the basic mechanism and its implication of such phenomena in the nervous system bears fundamental importance and requires preemptively the connectome information of a given nervous system. Inspired by these necessities of developing a theoretical and computational model to this end and, however, in the absence of connectome information for the inferior olive nucleus, here we investigated interference phenomena of the subthreshold oscillations in the reference system Caenorhabditis elegans for which the structural anatomical connectome was completely known recently. We evaluated how strongly the sinusoidal wave was transmitted between arbitrary two cells in the model network. The region of cell-pairs that are good at transmitting waves changed according to the wavenumber of the wave, for which we named a wavenumber-dependent transmission map. Also, we unraveled that (1) the transmission of all cell-pairs disappeared beyond a threshold wavenumber, (2) long distance and regular patterned transmission existed in the body-wall muscles part of the model network, and (3) major hub cell-pairs of the transmission were identified for many wavenumber conditions. A theoretical and computational model presented in this study provided fundamental insight for understanding how the multi-path constructive/destructive interference of the subthreshold oscillations propagating on electrically coupled neural networks could generate wavenumber-dependent synchronized rhythmic activity.
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- Developmental Biology
- Physics of Living Systems
Shape changes of epithelia during animal development, such as convergent extension, are achieved through the concerted mechanical activity of individual cells. While much is known about the corresponding large-scale tissue flow and its genetic drivers, fundamental questions regarding local control of contractile activity on the cellular scale and its embryo-scale coordination remain open. To address these questions, we develop a quantitative, model-based analysis framework to relate cell geometry to local tension in recently obtained time-lapse imaging data of gastrulating Drosophila embryos. This analysis systematically decomposes cell shape changes and T1 rearrangements into internally driven, active, and externally driven, passive, contributions. Our analysis provides evidence that germ band extension is driven by active T1 processes that self-organize through positive feedback acting on tensions. More generally, our findings suggest that epithelial convergent extension results from the controlled transformation of internal force balance geometry which combines the effects of bottom-up local self-organization with the top-down, embryo-scale regulation by gene expression.