Document Type and Release Option
Thesis (restricted to Georgia Southern)
A stroke occurs every 40 seconds in the United States. While lifestyle factors increase predisposition, genetics could also contribute. Integrins are cellular adhesion molecules that help with migration, differentiation, and cell organization in the extracellular matrix. This makes integrins vital to processes like vasculogenesis and angiogenesis. A specific integrin, ITGA6, is higher in preliminary developmental tissues, and elevated ITGA6 has shown to increase tumor metastasis and angiogenesis. Given the angiogenic and vasculogenic capabilities, ITGA6 is thought to influence stroke. A single nucleotide polymorphism of the ITGA6 gene was correlated with cerebrovascular hemorrhaging in stroke patients. Knocking down itga6 in zebrafish resulted in decreased neurovascular development showing dilation, hemorrhaging, fewer CtAs, and more protrusions. However, molecular mechanisms of ITGA6 in neurovascular development are not fully understood. A domain analysis of ITGA6 protein was performed with a zebrafish model. Gain-of-function and rescue ability of Full-length (FL), N-terminal and C-terminal domains of zebrafish and human integrin alpha 6 were investigated in zebrafish embryos. Zebrafish FL, N-terminal, C-terminal domain overexpression did not produce adverse phenotypes compared to control embryos. Zebrafish FL Itga6 rescued neurovascular defects induced by Itga6 knock-down. Thus, human ITGA6 domain constructs were tested for gain-of-function and rescue ability. Interestingly, human FL and N-terminal ITGA6 domains rescued neurovascular defects induced by the knockdown of zebrafish Itga6. This indicates the NTM domain might carry the functional abilities of ITGA6 to form blood vessels, while TMC does not. This creates a novel model to test the role of human integrins in vascular development.
Siclare, Benjamin D., "Role of Integrin alpha 6 (ITGA6) in Neurovascular Development and Stroke" (2019). University Honors Program Theses. 442.