Wednesday, May 23, 2018

Too Much or not Enough: Imaging Blood Vessel Growth and Regression in Zebrafish Embryos

Blood vessel growth, otherwise known as angiogenesis, is a central feature of embryonic development. If the vasculature system does not form properly it’s "game over" for the embryo. Blocking angiogenesis leads to impairment of development and ultimately death. Proper assembly of the circulatory system is critical for survival of an organism, as a functional vascular system is necessary to supply nutrients and oxygen to tissue and efficiently remove metabolic byproducts.

In the adult, angiogenesis is limited to particular instances such as hair growth, ovarian and endometrial cycles, and wound healing. However, angiogenesis is also associated with a number of pathologies including cancer, inflammation, and ischemic heart disease. In 1971 Judah Folkman, now known as the father of angiogenesis, discovered that blood vessel growth is a vital process for the survival and proliferation of solid tumors. Without a properly functioning vasculature system, tumors will cease to grow; thus, the aim of certain cancer therapeutics is to block tumor angiogenesis. However, in cases such as tissue repair after ischemic injury, the goal is to induce blood vessels to grow into the damaged area. Proper angiogenesis is a sometimes a precarious balancing act between too much and not enough.

The discovery of mechanisms behind blood vessel formation and regression is essential for cancer (and other) therapeutics. Zebrafish embryos are a great model for studying and imaging angiogenesis due to their small size, optical clarity, and the similarity of their vascular system to that of humans. (Yes, you are a lot more similar to a zebrafish than you might think!). The movies shown below highlight the difference between normal vascular development in a 1 day old zebrafish (Movie 1) with that of a zebrafish embryo treated with the angiogenic inhibitor SU5416 (Movie 2). SU5416 acts by inhibiting vascular endothelial growth receptor (VEGFR) and as you can see in Movie 2, vascular growth is restricted in this embryo. Zebrafish tail vasculature is marked with kdrl:mcherry, and these images were taken on the Cytation™ 5 as 10x stacks taken every 45 minutes for 24 hours.


Movie 1: Unperturbed zebrafish angiogenesis


Movie 2: Zebrafish treated with 2.5 ug/mL SU5416

By: BioTek Instruments, Sarah Beckman, PhD., Microscopist

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