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The role of [beta]1 integrins in dorsal aorta vasculogenesis in the chicken embryo

University of British Columbia

Vasculogenesis is the de novo formation of blood vessels from endothelial cell precursors known as angioblasts. In the chicken embryo, the dorsal aorta is formed by this process. Adhesion molecules such as integrins and their extracellular matrix ligands are believed to mediate vasculogenesis. Immunohistochemistry was used to determine the temporal and spatial distribution of the α5, α6 and β1 integrin subunits, the extracellular matrix proteins, fibronectin and laminin, and the endothelial cell marker, thrombomucin, in the chicken embryo from stages 8 through 14. The β1, integrin subunit and fibronectin were shown to be localized to the site of dorsal aorta vasculogenesis prior to lumen formation. The α5 integrin subunit and laminin were shown to be localized to the site of dorsal aorta vasculogenesis after lumen formation had commenced. The α6 subunit was not detected on cells of the dorsal aorta at the stages examined but was detected in control tissues. In order to investigate the role of β1 integrins in dorsal aorta vasculogenesis, integrin blocking antibodies and peptides containing integrin recognition sequences were injected at the site of dorsal aorta vasculogenesis in ovo to disrupt receptor-ligand interactions. The β1 integrin blocking antibodies, CSAT and W1B10, prevented dorsal aorta lumen formation and induced lateral displacement of somites while non-specific antibodies had no effect. None of the α5β1, α2β1, or α6β1 blocking peptides (RGD, DGEA, and YIGSR, respectively) or the control peptide, RGES, induced dorsal aorta malformations. The dorsal aorta malformations induced by blocking the β1 integrin subunit were proposed to be mediated by integrins other than α5β1, and α6β1 due to the absence of the α5 and α6 subunits during lumen formation. For the same reason, the ligands of the β1 integrins involved in dorsal aorta vasculogenesis would not include laminin; however, fibronectin remained as a possible ligand. Conversely, the localization of the β1 subunit along cell-cell contacts of angioblasts suggests that the ligand may be a cell membrane-bound molecule rather than an ECM component.

Thesis/Dissertation

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2009-05-26

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http://hdl.handle.net/2429/8299

Anatomy, Cell Biology and Physiology

University of British Columbia

UBCV

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