De Gennes, Marc;
(2022)
From cell fate dynamics to tissue organisation: Pattern formation by morphogen gradients.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
In this thesis, we present work on the formation of pattern in tissues. The literature distinguishes two classes of pattern formation mechanisms : positional information where cells read out an external cue and differentiate accordingly to form a pattern, and self-organization where the pattern emerges from the local interaction between cells. The vectors of these patterning mechanisms are morphogens, signaling molecules that activate cells in a concentration dependant manner. In a first part, we develop a model of morphogen gradient formation. Such morphogen gradients, produced in a source, are the external cues that give cells positional information about their location in a tissue. Our model describes a diffusive particle that can bind cell surface receptors, and leak into an external fluid. It accounts for experimental gradients observed in the developing Drosophila wing disc, and dismisses other mechanisms of gradient formation proposed in the literature. In a second part, we develop a model for the formation of the vein pattern of the Drosophila wing. The model is discrete and describes the evolution of the fate of interacting cells in a tissue. In its continuous limit, the model is a reaction diffusion equation, and theoretical results on the stability of stripes can be obtained. Advanced analytical tools yield single cell dynamics of shape and signals, and make precise comparison between model and experiments. Finally, in the spirit of having a strong link between experiment and theory, we develop simulations of vein patterning directly on experimental data from the fruit fly wing. We demonstrate that the vein patterning mechanisms reads a rough and noisy pre-pattern, and "self-refines" it into thin stripes. It therefore makes use of both modes of pattern formation that are positional information and self-organization.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | From cell fate dynamics to tissue organisation: Pattern formation by morphogen gradients |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2022. 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. |
| UCL classification: | 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 UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10143202 |
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