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TOOLBOX: In Living Color by Megan Scudellari
Researchers watch a heart grow, one vibrant cell at a time.
A tiny zebrafish has just hatched from its egg. Under a microscope, the slim, translucent fish lies motionless on its side, too young even to swim. The only movement is its beating heart—a pulsating blob of colorless muscle, with just the slightest hint of pink blood pooling at its base.
Kenneth Poss, an HHMI early career scientist at Duke University, bends over the microscope to peer at the heart. At this early stage of life, the single ventricle of the fish’s heart, a contracting chamber that pumps blood to the rest of the body, is a hollow tube composed of only about 120 muscle cells. Within three months, those cells, called cardiomyocytes, will replicate, morph, and spread to form a full-sized adult heart—a dramatic transformation that Poss recently visualized using a colorful new cell-labeling technique.
Poss, a soft-spoken scientist with an easy smile, normally studies adult zebrafish, not embryos or juveniles. For years, he has investigated the zebrafish’s expert ability to regenerate—to repair an amputated fin, injured retina, damaged spinal cord, and more. In 2002, Poss and colleagues demonstrated that zebrafish can fully regenerate their hearts even when as much as 20 percent of the heart muscle is removed. Humans, on the other hand, have a very limited ability to regenerate heart tissue: though scientists have discovered stem cells in the human heart, cardiomyocyte renewal occurs at a rate of only about 1 percent per year, a rate that declines as we age. Thus, after damage, the heart typically forms scar tissue, rather than repairing itself.
But in 2007, Poss heard about a new technique that temporarily shifted his focus to developing fish, rather than adult fish. Researchers at Harvard University had created a tool—which they gave the whimsical name “Brainbow”—to visualize mouse brain cells by labeling them with a rainbow of colors. Typically, scientists can track only a single cell at a time in a live mouse, fish, or fruit fly. But with the new technique, the Harvard team could follow hundreds of neurons in a live mouse brain simultaneously.
Poss wondered if it might be possible to adapt the technique to track cardiomyocytes in zebrafish. He began by using it to follow how a zebrafish heart develops after fertilization, hoping to uncover clues about how vertebrates, from fish to humans, build complex organs from just a few cells. “Studying how the heart is built during development is a great way to understand how to build it later in life, if you want to, say, reconstruct heart muscle after a heart attack,” he says.