Fine-tuning blood vessel development

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dc.contributor.advisorChilds, Sarah J
dc.contributor.authorWatterston, Charlene
dc.contributor.committeememberBrook, William J
dc.contributor.committeememberHuang, Peng
dc.contributor.committeememberBonni, Shirin
dc.contributor.committeememberYelon, Deborah
dc.dateWinter Conferral
dc.date.accessioned2021-11-19T22:03:01Z
dc.date.available2021-11-19T22:03:01Z
dc.date.issued2020-09-11
dc.description.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.
dc.identifier.citationWatterston, C. (2020). Fine-tuning blood vessel development (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/39388
dc.identifier.urihttp://hdl.handle.net/1880/114124
dc.language.isoenen
dc.language.isoEnglish
dc.publisher.facultyGraduate Studiesen
dc.publisher.facultyCumming School of Medicine
dc.publisher.institutionUniversity of Calgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.en
dc.subjectSignaling
dc.subjectZebrafish
dc.subjectVessels
dc.subjectAngiogenesis
dc.subjectEndothelial Cells
dc.subjectVascular Smooth Muscle Cells
dc.subjectDevelopmental Biology
dc.subject.classificationBiology--Cell
dc.subject.classificationBiology--Genetics
dc.subject.classificationBiology--Molecular
dc.titleFine-tuning blood vessel development
dc.typedoctoral thesis
thesis.degree.disciplineMedicine – Biochemistry and Molecular Biology
thesis.degree.grantorUniversity of Calgaryen
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameDoctor of Philosophy (PhD)
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