Mathematical modelling of Lymphangiogenesis
Mathematical modelling of Lymphangiogenesis
This thesis is concerned with lymphangiogenesis, the formation of new lymphatic vessels. The lymphatic system of a vertebrate is important for its homeostasis and immune responses to pathogens. Additionally, lymphangiogenesis is a means of cancer metastasis.
This thesis is concerned with how the vascular endothelial growth factor C (VEGFC) may regulate lymphangiogenesis in the zebrafish embryo.
We built a reaction-diffusion-convection model to describe the distribution of VEGFC in an idealised zebrafish trunk. We solved the model with the finite element method under a wide range of conditions. The results suggest that VEGFC can act as a morphogen for the progenitor cells of the lymphatic system: it induces their differentiation during lymphangiogenesis. However, it is unlikely to be a chemotactic factor which guides their migration. The abundance of collagen I in the trunk is the key regulator: it determines the dominant transport phenomenon and the extent of VEGFC-collagen I binding, thus
affecting the distribution of VEGFC. The abundance of collagen I is in turn regulated by the matrix metalloproteinase 2 (MMP2). Then, we simplified the model and studied it by Turing pattern analysis. The results suggest that VEGFC can form Turing patterns in the zebrafish embryo. However, further studies are needed before we can use this patterning mechanism to explain lymphangiogenesis.
Our conclusions about VEGFC can be tested experimentally. The demonstrated patterning mechanisms are not specific to VEGFC, MMP2, and collagen I; they can pattern other potential regulators of lymphangiogenesis, such as Cxcl12a; they can even be used to explain events other than lymphangiogenesis. Due to evolutionary conservation, they can be generalised to vertebrates other than the zebrafish too. The two mathematical models are new tools which will help in further studies about lymphangiogenesis and
other biological phenomena too.
University of Southampton
Wertheim, Kenneth Yann
55039b18-6290-4da7-9399-d678598cc781
March 2017
Wertheim, Kenneth Yann
55039b18-6290-4da7-9399-d678598cc781
Roose, Tiina
3581ab5b-71e1-4897-8d88-59f13f3bccfe
Wertheim, Kenneth Yann
(2017)
Mathematical modelling of Lymphangiogenesis.
University of Southampton, Doctoral Thesis, 234pp.
Record type:
Thesis
(Doctoral)
Abstract
This thesis is concerned with lymphangiogenesis, the formation of new lymphatic vessels. The lymphatic system of a vertebrate is important for its homeostasis and immune responses to pathogens. Additionally, lymphangiogenesis is a means of cancer metastasis.
This thesis is concerned with how the vascular endothelial growth factor C (VEGFC) may regulate lymphangiogenesis in the zebrafish embryo.
We built a reaction-diffusion-convection model to describe the distribution of VEGFC in an idealised zebrafish trunk. We solved the model with the finite element method under a wide range of conditions. The results suggest that VEGFC can act as a morphogen for the progenitor cells of the lymphatic system: it induces their differentiation during lymphangiogenesis. However, it is unlikely to be a chemotactic factor which guides their migration. The abundance of collagen I in the trunk is the key regulator: it determines the dominant transport phenomenon and the extent of VEGFC-collagen I binding, thus
affecting the distribution of VEGFC. The abundance of collagen I is in turn regulated by the matrix metalloproteinase 2 (MMP2). Then, we simplified the model and studied it by Turing pattern analysis. The results suggest that VEGFC can form Turing patterns in the zebrafish embryo. However, further studies are needed before we can use this patterning mechanism to explain lymphangiogenesis.
Our conclusions about VEGFC can be tested experimentally. The demonstrated patterning mechanisms are not specific to VEGFC, MMP2, and collagen I; they can pattern other potential regulators of lymphangiogenesis, such as Cxcl12a; they can even be used to explain events other than lymphangiogenesis. Due to evolutionary conservation, they can be generalised to vertebrates other than the zebrafish too. The two mathematical models are new tools which will help in further studies about lymphangiogenesis and
other biological phenomena too.
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WERTHEIM Final E-Thesis for E-Prints
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Published date: March 2017
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Local EPrints ID: 431494
URI: http://eprints.soton.ac.uk/id/eprint/431494
PURE UUID: d0b72bcb-85c6-4a7a-8581-666e88110f64
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Date deposited: 05 Jun 2019 16:30
Last modified: 16 Mar 2024 05:28
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Author:
Kenneth Yann Wertheim
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