How tadpoles make the leap to frogs

In his biology lab, he and his students are using a National Science Foundation grant to study the hormones that trigger the dramatic change called metamorphosis.

“The tail disappears, but not before tadpoles grow legs,” he said. “Their lungs get better. Their face is completely remodeled. They develop stereoscopic vision. About 90% of their digestive system disappears, but a stomach forms.

“Their immune system changes. Their hemoglobin changes. Even their eye pigment changes,” he said. “That’s why frog metamorphosis is a really good model to study hormones and development. It has such a dramatic effect.”

In his lab, Buchholz is using the gene-editing tool CRISPR to modify African clawed frogs, a species used as a model system in both biology and medicine. CRISPR allows researchers to change particular strands of proteins that make up DNA.

In one experiment, Buchholz prevented a developmental hormone called aldosterone from binding with its designated receptor. They expected that this might suspend metamorphosis.

What happened?

“The answer is nothing. We looked so hard at the phenotype. But nothing changed,” he said.

Buchholz said it’s likely that multiple related hormones serve duplicate roles, allowing development to proceed even in the absence of one.

“A lot of times you have a mutation but it can be compensated for by other proteins,” he said. “Cancer is that way. You make one mutation in a cell, you won’t get cancer. It takes a series of multiple mutations where that cell is no longer regulated.”

Through the NSF grant, Buchholz and his students next will target multiple hormones to determine their role in metamorphosis.

“It’s a very complicated system. So the question is how do we figure out what’s going on?” Buchholz said.

While frogs and people seem to have little in common, newborn babies undergo dramatic changes at birth when their umbilical cord is cut and their digestive and circulatory system is suddenly independent from their mom’s. At birth, a flap in the heart closes to send blood to the lungs. They must take in nutrition through their digestive system. And suddenly they have to regulate their own body temperature, Buchholz said.

Likewise, we still have much to learn about the role hormones play in regulating our own growth, development and immune systems, among other processes.

“The more we can learn about frogs, the more we can learn about ourselves. And those are compelling reasons to study animals,” he said.

Featured image at top: African clawed frogs are a model system in medicine and biology. Photo/Andrew Higley/UC Marketing + Brand