Zebrafish, the Living Looking Glass
Young zebrafish have clear skin, creating living windows for reproductive growth. Zebrafish sex organs can be modified to glow in UV light, which helps us study diseases like cancer. The roundworm genome contains 1.5 billion DNA base pairs.
In the basement of the Life Sciences Building, around 1,500 fish tanks, ranging in size from briefcases to small crates, are systematically laid out in rows on metal shelves. From fertilized egg to adult, the roughly 20,000 fish represent the entire zebrafish lifecycle, providing Bruce Draper with a comprehensive view of their growth.
“If you’re looking at the process of development—so going from a fertilized egg to a swimming, feeding organism—all that process in mammals is happening in utero, so you actually have to sacrifice the mom to get the embryos out to study them,” says Draper. “With zebrafish, it’s all external fertilization.”
Part of Draper’s research focuses on problems of reproductive development. Zebrafish (Danio rerio) are well-suited for this research as their embryos are clear, providing a window into the biological machinery behind their formation. As the fish age, they develop stripes and lose their transparency.
Researchers bypass this problem by genetically modifying zebrafish with a gonad—the organ responsible for producing sperm and eggs—that glows under ultraviolet light. This allows continuous monitoring of gonad development as the fish grows, providing clues about reproductive development diseases like ovarian cancer.
Previously, Draper and his colleagues identified the gene fgf24 as important for gonad development in zebrafish. Mutant zebrafish developed defective gonads and had limited reproductive abilities. While this specific gene signaling isn’t known to be involved in mammalian gonad development, many aggressive ovarian cancers correlate with an overactive signaling pathway related to this gene. Overall, about 84 percent of the genes associated with human disease have counterparts in zebrafish.
Draper and his colleagues are investigating how single-cell RNA sequencing could help advance their research. The technique allows a high-resolution view of individual cells and the genes they express.
“We’re now identifying on a much more refined level what genes are expressed in particular cells,” he says, noting that the most aggressive forms of ovarian cancer typically occur in the organ’s cell linings. “We’re very interested in trying to identify those epithelial cells in our dataset so that we can start asking what other genes are expressed in there.”