The University of Southampton
University of Southampton Institutional Repository

Mathematical modelling of Lymphangiogenesis

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
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.

Text
WERTHEIM Final E-Thesis for E-Prints - Version of Record
Available under License University of Southampton Thesis Licence.
Download (8MB)

More information

Published date: March 2017

Identifiers

Local EPrints ID: 431494
URI: http://eprints.soton.ac.uk/id/eprint/431494
PURE UUID: d0b72bcb-85c6-4a7a-8581-666e88110f64
ORCID for Tiina Roose: ORCID iD orcid.org/0000-0001-8710-1063

Catalogue record

Date deposited: 05 Jun 2019 16:30
Last modified: 06 Jun 2019 04:01

Export record

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×