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Title: Mathematical modelling of lymphangiogenesis
Author: Wertheim, Kenneth Yann
ISNI:       0000 0004 7967 041X
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 2017
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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.
Supervisor: Roose, Tiina Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available