Fluorescent Fish Genes Could Help Uncover Source of Pediatric Cancer

A transgenic zebrafish that produces fluorescent tags in migratory embryonic nerve precursor cells could help lead researchers to the origins of neuroblastoma, a pediatric cancer in which malignant cells form in immature nerve tissue.

Undergraduate Sarah Downing (left) and neurodevelopmental biologist Rosa Uribe conduct research in the Uribe Lab at Rice University. Courtesy of Jeff Fitlow/Rice University.

The zebrafish line, created by researchers from Rice University, the University of Illinois at Chicago, and California Institute of Technology, produces fluorescent tags that glow in different colors based on the behavior of a gene called SOX10 that is active in neural crest cells — transient embryonic stem cells that give rise to many cell types in the body. Finding the "off" switch for SOX10 in neural crest cells could potentially lead to treatments for cancers where SOX proteins play a role, said researcher Rosa Uribe.

Uribe’s lab uses seven microscopes capable of gathering time-lapse images of the glowing cells, including a robotic instrument with tiny hoses and pumps that can draw a single embryo from a numbered test chamber up through a hose, transport it to the microscope focal plane, bring it into focus, rotate it for photos from any angle, and then return it. It can repeat the process for up to 95 more embryos.

“For the migration time-lapse images there is software that’s capable of following individual cells for hours,” Uribe said. “We can get angles and trajectories, maps of routes taken by one cell or groups of cells, and we can get quantitative data, like velocities and proliferation rates.”

The research was published in Genesis (doi:10.1002/dvg.23214).

Neural crest cells migrate extensively during embryonic development. Thanks to a transgenic zebrafish with fluorescent reporter genes, researchers can watch as neural crest cells migrate in a 1-day-old embryo. Red cells are replicating their DNA, and green cells are about to divide. The time-lapse is overlaid onto an image of the embryo (white), which shows the neural crest cells migrating extensively along a region of the developing embryo that will eventually become the fish’s neck. The new zebrafish reporter line could help researchers find the origins of neuroblastoma, a pediatric cancer that develops from neural crest cells. Courtesy of Uribe Lab/Rice University.