Understanding the interactions between Neuropilin-1 and Neuropilin-2 during developmental angiogenesis

Cardwell-Brown, Alfie (2022) Understanding the interactions between Neuropilin-1 and Neuropilin-2 during developmental angiogenesis. Masters thesis, University of East Anglia.

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Angiogenesis is the process by which new vessels form from pre-existing vasculature and is a crucial process during embryogenesis. However, dysregulation of angiogenesis can lead to vasculature irregularities resulting in pathologies such as tumor formation. Angiogenesis is known to be stimulated by various pro-angiogenic factors, such as VEGF, that activates signaling cascades involved with endothelial cell angiogenic mechanisms. It is known that VEGF-VEGFR2 binding mediates the internalization of the integrins α5β1 and αVβ3, which are integral to angiogenic regulation through the recruitment of focal adhesion proteins. Two co-receptors, NRP1 and NRP2 have been identified to form complexes with VEGFR2, increasing the receptor proteins affinity for VEGF and further regulating angiogenesis. In this way, it is hypothesized that a deletion of either NRP1 or NRP2 may hinder regulatory mechanisms controlling angiogenesis. This study therefore sets out to further investigate the effect of a singular NRP1 or NPR2 deletion, and to newly establish the effect of a deletion of both NRPs on endothelial cell processes involved with angiogenesis. Evidence found from in vitro immunocytochemistry experiments seem to confirm that a depletion of both NRPs reduces focal adhesion recruitment and increases focal adhesion maturation. Furthermore, a reduction in levels of both NRPs may also reduce actin cytoskeleton remodeling in response to pro-angiogenic signals. On top of this, in vitro experiments involving a depletion of both NRPs hint towards the establishment of an angiogenic compensatory mechanism to cope with the loss of both co-receptors. Initial in vivo tumour sectioning experiments have also provided data showing that blood vessel formation is reduced in lung carcinoma cells of mice with a depletion of both NRP1 and NRP2.

Item Type: Thesis (Masters)
Faculty \ School: Faculty of Science > School of Biological Sciences
Depositing User: Chris White
Date Deposited: 25 Apr 2023 07:36
Last Modified: 25 Apr 2023 07:36
URI: https://ueaeprints.uea.ac.uk/id/eprint/91871

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