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Leapfrog, scientist-style

Woods Hole center’s amphibians hold promise for helping humans regrow organs

Xenopus laevis, a South African frog, is prized by scientists because it has the ability to regrow the lens of its eye and lays eggs that are big enough for scientists to study and manipulate. Xenopus laevis, a South African frog, is prized by scientists because it has the ability to regrow the lens of its eye and lays eggs that are big enough for scientists to study and manipulate.
By Carolyn Y. Johnson
Globe Staff / September 6, 2010

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The South African frog known as Xenopus laevis first became a tool of medicine in the 1940s, when the females were used in hospitals worldwide for pregnancy tests: If injected with a pregnant woman’s urine, the frog laid eggs.

The aquatic amphibian is far more valuable now as a lab rat, used to study fundamental questions about the development of embryos.

Blessed with the unusual ability to regrow the lens of its eye, and laying eggs big enough to study and manipulate, the frog is prized by scientists who want to explore things as diverse as birth defects and organ regeneration.

But unlike other workhorses of science, the frogs did not have a real home base. Jackson Laboratory in Bar Harbor, Maine, maintains different genetic strains of lab mice. The Bloomington Drosophila Stock Center at Indiana University collects and distributes lines of fruit flies. And the Zebrafish International Resource Center in Oregon stocks the fish. Now, a five-year, $3.4 million grant from the National Institutes of Health will support a national Xenopus center at the Marine Biological Laboratory in Woods Hole.

“This is a major model for regenerative biology,’’ said Joshua Hamilton, MBL’s chief academic and scientific officer. “The fact is, humans don’t regenerate, and neither do mice and rats. But we do know these earlier or simpler forms of life can. The aspiration is if we can learn how these animals do this, we should be able to translate that to humans.’’

The 6-inch frog has many advantages for developmental biologists who study how embryos grow, not least the seemingly endless supply of eggs it can, with injection of a hormone, lay year-round. Amphibians in the United States and Europe typically lay eggs in the spring.

“The eggs are big, and development occurs outside the mother’s body,’’ allowing scientists to manipulate the egg and watch it develop, said Douglas Melton, a stem cell scientist at Harvard University who is now well known for his work on diabetes, but did work on Xenopus earlier in his career. He said that what is learned from the frog helps guide work by stem cell scientists today.

“What was discovered in frogs about signals that tell cells what to do is information we use every day, in guessing how to tell a stem cell what to do,’’ Melton said.

For scientists who study Xenopus, there are numerous reasons to work with the frog, and many said they are pleased there will now be a place that stocks the frogs. The Xenopus program is a cornerstone of the MBL’s Eugene Bell Center for Regenerative Biology and Tissue Engineering and will provide a resource for training and research.

Robert Grainger, a biologist at the University of Virginia and the principal investigator under the grant to establish a resource of Xenopus at MBL, studies development of the eye.

“Where Xenopus is simply spectacular is . . . being able to study how you make organs and the genes that control the formation of an organ,’’ Grainger said. “When you understand how to make an organ — for example, the pancreas — then you do have the raw material to do regenerative medicine.’’

Other scientists use the frog to study birth defects. Using a fast-developing species, Xenopus tropicalis, they study how mutations affect development.

Dr. Mustafa Khokha, a genetics and pediatrics professor at Yale University, uses genetic variants of frogs to try to understand which genes go awry and cause birth defects that affect their hearts or the formation of their heads and faces. He hopes to see whether analogous genes cause similar problems in humans.

“We cannot perturb the human being, so we try to do it in a model system,’’ Khokha said.

Hazel Sive, a member of the Whitehead Institute for Biomedical Research in Cambridge and a biologist at the Massachusetts Institute of Technology, said the frog offers a chance to probe a wide range of questions, from early development to the spread of cancer.

Because there are parallels between tumor metastasis and embryonic processes, she said, it is possible to use the embryo as a surrogate for cancer, to better understand which genes are involved.

A frog may seem like an odd organism to investigate in the hopes of getting clues about the biology of people and human disease, but the species are more similar than one might think. This year, the Xenopus tropicalis genome was published in the journal Science.

“One of the key conclusions of the article,’’ Grainger said, “was how strikingly similar the organization of genes in frogs is to humans and mice.’’

Carolyn Y. Johnson can be reached at cjohnson@globe.com.

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