Zebrafish Model Provides Clues to Arterial Development

Researchers have utilized transgenic zebrafish embryos with fluorescently labeled blood vessels to identify and characterize a mutant fish (y10) that lacks the gene for synthesis of phopholipase C gamma-1 protein (Plcg1) and displays specific defects in the formation of arteries but not veins.

Investigators at the US National Institutes of Health (Bethesda, MD, USA) worked with transparent zebrafish embryos, a well-established model system for development of vertebrates. By labeling blood vessels with a fluorescent marker they could observe vessel formation during development. Their report in the June 1, 2003, issue of Genes & Development described the y10 mutant, which appeared to lack arteries but had ostensibly normal veins. The gene responsible for the y10 mutant phenotype was found to code for Plcg1, a known effector of receptor tyrosine kinase signaling found in a number of vertebrate species, including mammals.

The y10 mutant embryos failed to respond to added vascular endothelial growth factor (Vegf), indicating that Plcg1 functioned specifically downstream of the Vegf receptor during embryonic development to govern formation of the arterial system.

First author Dr. Nathan Lawson, now an assistant professor of molecular medicine at the University of Massachusetts Medical School (Worcester, USA; www.umassmed.edu) explained, "Until recently, we really did not know what the signals were that determined artery and venous identity, or even that this process was governed by genetic signals. It was always thought that circulatory flow and pressure caused a blood vessel to be an artery or a vein. I think an important implication of this work is that the signals that drive this process appear to be the same in fish and mammals. For that reason we think it is likely that what we learn about zebrafish blood vessels may help us manipulate the growth of human blood vessels in a variety of disease processes, including diabetes and cancer.”





Related Links:
National Institutes of Health
University of Massachusetts Medical School