Fixing a Deformed Frog Face
Air Date: Week of May 18, 2012
Researchers found that tadpoles have the ability to regenerate parts of their bodies damaged during development. Now they’re trying to determine how that mechanism can be applied to human development. Biologist Laura Vandenberg of Tufts University tells host Bruce Gellerman about the breakthrough
GELLERMAN: From the Jennifer and Ted Stanley Studios in Somerville Massachusetts it’s Living on Earth. I’m Bruce Gellerman. Inside the developing embryo is the genetic blueprint that determines how the baby will turn out. It’s a complex process, not well understood and sometimes things can go wrong. For example, defects of the face such as cleft lip and palate affect more than 1 in every 600 human births. The congenital malformations underscore one of the big questions in developmental biology: how do complex shapes like the face put themselves together?
In a laboratory at Tufts University scientists think they’ve got part of the answer. Using tadpoles as a model, researchers have identified a “self-correcting” mechanism by which developing frogs recognize and repair head and facial abnormalities. The team has published its finding in the latest edition of the journal Developmental Dynamics. Laura Vandenberg is one of the authors:
VANDENBERG: A little while ago we had done a study that showed that there's a bio-electrical control of how the face develops. So what we did was look at frog tadpoles as their face is forming, and we found in areas where the eye will form, the nose will form, the mouth will form, there’s a flash of bioelectrical activity.
So, prior to those cells knowing that they should make an eye, they are different from their neighbors in terms of their bioelectrical properties.
GELLERMAN: What triggers the bioelectric charge?
VANDENBERG: So, in every cell of our bodies, there are little pumps and channels that are responsible for the flow of ions. So, that’s things that are positively charged, like a potassium ion, or a hydrogen ion—or things that are negatively charged, like chloride ions. And so these flow in and out of our cells and they change the bioelectrical properties of cells because they’re charged molecules. And what we found is that if we alter a pump in certain cells that we can change the way that the face develops.
GELLERMAN: So, the pump changes the flow of the ions?
VANDENBERG: That’s right. So if we block this pump from acting, then, normally hydrogen ions are pumped out of the cell, and we can prevent that from happening so that the cells stay more positively charged.
GELLERMAN: So you can change the development of a tadpole’s face and head?
VANDENBERG: That’s right. Just by changing the flow of ions. Not by changing a gene necessarily. So you can do this by treating them with a drug that affects ion flow, or by changing an RNA that affects ion flow.
GELLERMAN: Now, we know that frogs and tadpoles can regenerate, you know, cut off their tail, new tail. We can’t do that...
VANDENBERG: That’s right.
GELLERMAN: Does this have any application for people?
VANDENBERG: So, there is some regenerative capability in people. So your liver can regenerate; actually from a very small piece, it can regenerate. And one thing that you probably didn’t know is that children’s fingertips can regenerate. So if a child below the age of seven looses the tip of their fingertip and you leave the wound open so that the electrical flow can flow out of that wound, the fingertip can regenerate.
GELLERMAN: So the implications of your work are potentially profound.
VANDENBERG: Yes, and the really cool thing, if you think about it, is that if you need bioelectrical properties to build a normal face, perhaps a birth defect like cleft palate could be fixed by altering bioelectrical properties. Now, how would you do such a thing? Gene therapy for the most part has failed in humans—it has all kinds of problems associated with it, including the development of cancers in children who are treated with gene therapy.
But if you can use a drug that affects bioelectrical properties, then you could treat a fetus with a drug. So are the drugs that we’re talking about? The kind of drugs that we know are already safe for people to use—the kinds of drugs that affect bioelectrical properties of our gut when we make too much acid in our gut.
GELLERMAN: So where do you go from here?
VANDENBERG: What we’d really like to know is: is this really something special about the frog face, or is this more generally acceptable or understandable to how other animals develop the parts of their face.
GELLERMAN: So in the lab, when you go back from the studio today, what are you going to do?
VANDENBERG: Well, so, that’s where the second part of our work really started to change how we were thinking about things. We went and we looked at these animals that we have produced that have malformed faces, and we watched them develop over time and we saw the most fascinating thing. These animals can actually fix, on their own, problems with their faces. So they can repair a totally deformed face, by just giving them enough time.
GELLERMAN: So there’s a feedback mechanism. Something is triggering the deformity, something is telling them to change and repair - and they do it!
VANDENBERG: That’s right. So we trigger the deformity, but the animal can somehow sense: this isn’t right. And I need to fix it.
GELLERMAN: So if a child had a cleft palate, how come they aren’t getting a triggering mechanism saying hey, now repair that cleft palate?
VANDENBERG: So, perhaps this is also why we can only repair our fingertips for the first few years of life, or why our bodies don’t regenerate certain tissues. So if we could stimulate the pathway that’s regenerating and repairing in a frog…in a child…it has huge implications for dealing with children who have these deformities that currently can only be fixed by surgery.
GELLERMAN: Dr Vandenberg, thank you for coming in.
VANDENBERG: Thank you.
GELLERMAN: Laura Vandenberg is a developmental biologist at Tufts University.
[MUSIC: Bjork “Pagan Poetry” from Vespertine (Electra Records 2004)]
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