Term of Award

Fall 2015

Degree Name

Master of Science in Biology (M.S.)

Document Type and Release Option

Thesis (restricted to Georgia Southern)

Copyright Statement / License for Reuse

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

Department

Department of Biology

Committee Chair

Vinoth Sittaramane

Committee Member 1

Christopher Cutler

Committee Member 2

John Scott Harrison

Abstract

Stroke is one of leading causes of death and disability worldwide (CDC, 2014). Hemorrhagic stroke could be due to defective neurovascular development. Even though the occurrence of stroke happens in older age groups, genetic studies have found mutations (SNPs) in human integrin alpha 6 (ITGA6) linked to the predisposition of stroke. As of now, the roles of ITGA6 in the development of the neurovascular system are unknown. This study created itga6 deficient embryos using antisense nucleotides to investigate neurovascular development in zebrafish embryos using appropriate vascular transgenic lines. Deficiency in itga6 leads to severe loss of central arteries (CtAs), increase in endothelial cell protrusions, and dilation of several hindbrain blood vessels such as the basal artery (BA) and primordial hindbrain channels (PHBC). Itga6 mRNA injections were able to rescue deficient phenotypes, displaying return in number of CtAs, decrease in protrusions, and decrease in dilation. Further, time-lapse analysis also supported these findings in the deficient embryos showing an increase in endothelial protrusions with inability to make connections as seen in the controls. The loss of itga6 in embryos also displayed hemorrhaging in the hindbrain by 48hpf. These results indicate that itga6 does play a critical role in neurovascular formations. Itga6 is a transmembrane receptor for the extracellular matrix protein laminin enabling matrix remodeling during morphogenetic processes. During cancer metastasis Itga6 has been shown to cleave extracellularly allowing for cell migration. This study investigated whether integrin alpha 6’s ability to cleave is also required for neurovascular development. It was found that this cleavage mechanism in integrin alpha 6 is necessary for the CtA formation in the hindbrain.

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