Fine-tuning blood vessel development
AdvisorChilds, Sarah J
Committee MemberBrook, William J
Vascular Smooth Muscle Cells
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AbstractBlood vessel development is typically characterized by stages marking the growth and gradual refinement of vascular networks. Understanding how these stages integrate is essential to our understanding of how the early signals which control vessel growth can influence later stages of vessel stabilization. In this thesis, I use a zebrafish model (Danio rerio) to explore the roles of two negative regulators that modulate key signaling pathways controlling vessel growth. At the early stages, the initial growth of vessels is carefully controlled by distinct gene expression patterns. As a vessel forms, in response to the attractive Vascular endothelial growth factor (Vegf) pathway, its sprouting is often opposed by repulsive Semaphorins (Semas) which limit directional growth. I investigated the role of semaphorin3fb (sema3fb) which I found to be expressed within developing endothelial cells of the zebrafish embryo. I found that sema3fb likely acts through auto-secretory feedback to modulate Vegf responses to promote appropriate vessel growth. At later stages, a supportive layer of vascular smooth muscle cells (vSMCs) is recruited to form the contractile layer of the vessel wall. Bone morphogenic protein (Bmp) signaling is implicated in cellular crosstalk from the underlying endothelium to vSMCs which is critical to the structural integrity of a blood vessel. I investigated the microRNA26a (miR26a), which I found enriched in the endothelial lining of the blood vessel. I identified a non-autonomous role for miR26a in regulating Bmp signaling through its effector Smad1 to control vSMC maturation. Together my work offers mechanistic insight into the cellular communication pathways that regulate blood vessel formation and focuses on how both internal and external signaling pathways communicate to promote vessel formation.
CitationWatterston, C. (2020). Fine-tuning blood vessel development (Unpublished doctoral thesis). University of Calgary, Calgary, AB.
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