Ioannou, Elena;
(2023)
Investigating the role of NRP1 in vascular patterning.
Doctoral thesis (Ph.D), UCL (University College London).
Abstract
Defective cardiovascular development can cause congenital heart defects. The transmembrane protein NRP1 promotes the remodelling of the foetal cardiac outflow tract into the base of the pulmonary artery and aorta and the remodelling of the primitive pharyngeal arch arteries (PAA) into the great vessels of the heart. However, outstanding questions remain concerning: (1) the temporal window in which NRP1 enables PAA morphogenesis, (2) the specific cell types that require NRP1 for PAA morphogenesis, (3) the NRP1 ligand(s) that promote PAA morphogenesis and (4) whether NRP1 acts together with its co-receptor PLXND1 to promote PAA morphogenesis. During my PhD, I used genetically modified mice in combination with wholemount immunofluorescent staining, sophisticated imaging and 3D rendering to examine the role of NRP1 and its ligands and co-receptors during PAA morphogenesis. I found that: (1) loss of NRP1 resulted in a reduction of the number of endothelial cells in the pharyngeal arch and that those present fail to coalesce into the 4th PAA, (2) NRP1 is required in the SHF-derived endothelium but not in NCC for the 4th PAA formation, (3) NRP1 is required for smooth muscle formation around the PAA and subsequent remodelling into the great vessels and (4) PLXND1 is necessary but not the ligands VEGF and SEMA3, during PAA formation.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Investigating the role of NRP1 in vascular patterning |
| Language: | English |
| Additional information: | Copyright © The Author 2023. 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 UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10183748 |
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