Bubna-Litic, Matyas;
(2025)
Mechanical regulation of mesodermal fate specification in response to morphogen induction.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
The vertebrate body plan arises from morphogenetic movements and specification of germ layers during gastrulation. It has long been appreciated that morphogenetic movements depend on prior physical environment and geometry as well as emergent properties of cells and cell collectives. Evidence for mechanotransduction in vitro and in vivo points to a dynamic and complex interaction between morphogenesis and fate specification. Yet the interplay between tissue mechanics and morphogen signalling is still poorly understood as prior studies have mostly focused on the role of either chemical or mechanical signals in a particular developmental context. Here I show that the classical experimental system to produce Xenopus gastruloid-like structures by treatment with a single mesoderm-inducing morphogen, Activin, can be used to investigate the interplay of a chemical signal with mechanical stimulation. I present a method, suitable for live imaging, where explants are mechanically stimulated by uniaxial compression. Mechanical stimulation during Activin induction leads to a modulation of the observed effect of the biochemical input where explant elongation and axial patterning is altered. Evidence presented here indicates a novel role of tissue mechanics in the β-catenin-dependent induction of the head organiser ex vivo. Increase in blastocoel volume and vegetal rotation combined with convergent extension during pre-gastrulation epiboly have been proposed and perturbed as sources of mechanical cues in vivo. This work implies that to understand embryonic induction, morphogenesis and tissue mechanics must be considered in our models. Appreciation of mechanochemical signalling has the potential to unlock more biologically relevant and robust synthetic organoid systems and reveal new mechanisms in vertebrate development.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Mechanical regulation of mesodermal fate specification in response to morphogen induction |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2025. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| Keywords: | Embryonic induction, Tissue mechanics, Head organiser, Developmental mechanobiology |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10208477 |
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