What can modern fish and salamander genes tell us about how our limbs evolved?

Sep 11, 2016

Have you ever watched a fish swim and thought that all of the long, tiny bones in its pectoral fin looked a bit — just a little bit — like fingers? Or seen a salamander that’s regrown its tail after a close call with a predator, and wondered why we can’t regenerate our limbs? As scientists learn more about the genes that shape animal musculoskeletal systems, they’re uncovering clues about how our own limbs developed — and may someday regenerate.

For instance, while it’s long been known that there are similarities between our arm bones and other bones in a fish’s fin, scientists once thought that the skinny, finger-like bones of the pectoral fin had been lost in our common ancestor.

Now, new research from the University of Chicago suggests that an evolutionary link does exist between fish fins and mammalian hands. In the study, researchers eliminated select Hox genes, which give segments in the body identity, from the genomes of zebrafish and mice. They found that the mutations led to a mouse limb with no fingers, and a zebrafish fin with significantly reduced fin bones.

Kim Cooper, a professor of biological sciences at the University of California-San Diego, says the study’s findings indicate that the genes to make long, pectoral-fin bones in fish may have been repurposed to make hands.

“If you think about building a building, instead of going and buying all new construction materials to make a hand, you’ve gone to the salvage yard and taken some of the information that was there in the fish to make a hand by similar processes,” Cooper says.

Meanwhile, researchers at the University of California-Irvine are wrapped up in another question about limbs — namely, if other animals can regenerate their limbs, why can’t we? Dr. David Gardiner, a professor of developmental and cell biology at University of California-Irvine, is looking for answers in the axolotl, a rare Mexican salamander that’s often studied in labs for its ability to regenerate.

“When we look around and see all these animals and plants and life forms on Earth, they have evolved for hundreds of millions … of years,” Gardiner says. “And so these experiments have been going on. So you look at an axolotl and it shows you that the mechanisms are there to regenerate, and they’ve discovered how to do it. So the answer is to tease out a part experimentally, and figure out what the steps are. And then once you know the steps, then we should be able to do that in humans.”

In a video for Science Friday, researchers at the University of California-Irvine illustrate how axolotls can even grow extra limbs, like a third arm. When a wound is grafted with skin from another area of the axolotl’s arm with a different positional value, the newly neighboring cells of the wound and graft can “fill in” what would normally lie between them, like an arm.

What we don’t know yet is why human cells can’t spur the same type of regeneration. Gardiner says that our cells may already have the information they need to regenerate, and for some reason aren’t acting on it.

“The Hox genes, for example, are very stable,” Gardiner says. “And they are very positionally expressed in humans. So we’re seeing that maybe the information is there. I personally would point out that it’s very difficult to distinguish between stimulation and dis-inhibition. So we keep thinking, well why can’t humans regenerate? But the other possibility is that we do regenerate, but it’s being repressed. … Because there’s so much regeneration everywhere in the animal world.”

Cooper adds that from an evolutionary perspective, this possibility is worth exploring further. “If you look at the evolution of regeneration, we do know that it was a loss in species that can’t regenerate and not something that’s special about an axolotl, for example.”

This article is based on an interview that aired on PRI's Science Friday.

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