Your Inner Fish: A Journey Into the 3.5-Billion-Year History of the Human Body by Neil Shubin Page A
Authors: Neil Shubin
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gene made one end of a body segment look different from the other. Fly geneticists named it hedgehog . Doesn’t the function of hedgehog in the fly body—to make one region different from another—sound like what the ZPA does in making the pinky different from the thumb? That parallel was not lost on the three labs. So off they went, looking for a hedgehog gene in creatures like chickens, mice, and fish.
Because the lab groups knew the structure of the fly’s hedgehog gene, they had a search image to help them single out the gene in chickens. Each gene has a distinctive sequence; using a number of molecular tools, the researchers could scan the chicken’s DNA for the hedgehog sequence. After a lot of trial and error, they found a chicken hedgehog gene.
Just as paleontologists get to name new species, geneticists get to name new genes. The fly geneticists who discovered hedgehog had named it that because the flies with a mutation in the gene had bristles that reminded them of a little hedgehog. Tabin, McMahon, and Ingham named the chicken version of the gene Sonic hedgehog, after the Sega Genesis video game.
Now came the fun question: What does Sonic hedgehog actually do in the limb? The Tabin group attached a dye to a molecule that would stick to the gene, enabling them to visualize where the gene is active in the limb. To their great surprise, they found that only cells in a tiny patch of the limb had gene activity: the ZPA.
So the next steps became obvious. The patterns of activity in the Sonic hedgehog gene should mimic those of the ZPA tissue itself. Recall that when you treat the limb with retinoic acid, a form of vitamin A, you get a ZPA active on the opposite side. Guess what happens when you treat a limb with retinoic acid, then map where Sonic hedgehog is active? Sonic hedgehog becomes active on both sides—pinky and thumb—just as the ZPA does when it is treated with retinoic acid.
Knowing the structure of the chicken Sonic hedgehog gave other researchers the tools to look for it in everything else that has fingers, from frogs to humans. Every limbed animal has the Sonic hedgehog gene. And in every single animal that we have studied, Sonic hedgehog is active in the ZPA tissue. If Sonic hedgehog hadn’t turned on properly during the eighth week of your own development, then you either would have extra fingers or your pinky and thumb would look alike. Occasionally, when things go wrong with Sonic hedgehog, the hand ends up looking like a broad paddle with as many as twelve fingers that all look alike.
We now know that Sonic hedgehog is one of dozens of genes that act to sculpt our limbs from shoulder to fingertip by turning on and off at the right time. Remarkably, work in chickens, frogs, and mice was telling us the same thing. The DNA recipe to build upper arms, forearms, wrists, and digits is virtually identical in every creature that has limbs.
How far back can we trace Sonic hedgehog and the other bits of DNA that build limbs? Is this stuff active in building the skeleton of fish fins? Or are hands genetically completely different from fish fins? We saw an inner fish in the anatomy of our arms and hands. What about the DNA that builds it?
Enter Randy Dahn with his mermaid’s purses.
GIVING SHARKS A HAND
Randy Dahn entered my laboratory with a simple but very elegant idea: treat skate embryos just the way Cliff Tabin treated chicken eggs. Randy’s goal was to perform all the experiments on skates that chicken biologists had performed on chicken eggs, from Saunders and Zwilling’s tissue surgeries all the way to Cliff Tabin’s gene experiments. Skates develop in an egg with a kind of shell and a yolk. Skates even have big embryos, just as chickens do. Because of these convenient facts, we could apply to skates many of the genetic and experimental tools people had developed to understand chickens.
What could we learn by comparing the development of a shark fin to that of a chicken leg?
Because the lab groups knew the structure of the fly’s hedgehog gene, they had a search image to help them single out the gene in chickens. Each gene has a distinctive sequence; using a number of molecular tools, the researchers could scan the chicken’s DNA for the hedgehog sequence. After a lot of trial and error, they found a chicken hedgehog gene.
Just as paleontologists get to name new species, geneticists get to name new genes. The fly geneticists who discovered hedgehog had named it that because the flies with a mutation in the gene had bristles that reminded them of a little hedgehog. Tabin, McMahon, and Ingham named the chicken version of the gene Sonic hedgehog, after the Sega Genesis video game.
Now came the fun question: What does Sonic hedgehog actually do in the limb? The Tabin group attached a dye to a molecule that would stick to the gene, enabling them to visualize where the gene is active in the limb. To their great surprise, they found that only cells in a tiny patch of the limb had gene activity: the ZPA.
So the next steps became obvious. The patterns of activity in the Sonic hedgehog gene should mimic those of the ZPA tissue itself. Recall that when you treat the limb with retinoic acid, a form of vitamin A, you get a ZPA active on the opposite side. Guess what happens when you treat a limb with retinoic acid, then map where Sonic hedgehog is active? Sonic hedgehog becomes active on both sides—pinky and thumb—just as the ZPA does when it is treated with retinoic acid.
Knowing the structure of the chicken Sonic hedgehog gave other researchers the tools to look for it in everything else that has fingers, from frogs to humans. Every limbed animal has the Sonic hedgehog gene. And in every single animal that we have studied, Sonic hedgehog is active in the ZPA tissue. If Sonic hedgehog hadn’t turned on properly during the eighth week of your own development, then you either would have extra fingers or your pinky and thumb would look alike. Occasionally, when things go wrong with Sonic hedgehog, the hand ends up looking like a broad paddle with as many as twelve fingers that all look alike.
We now know that Sonic hedgehog is one of dozens of genes that act to sculpt our limbs from shoulder to fingertip by turning on and off at the right time. Remarkably, work in chickens, frogs, and mice was telling us the same thing. The DNA recipe to build upper arms, forearms, wrists, and digits is virtually identical in every creature that has limbs.
How far back can we trace Sonic hedgehog and the other bits of DNA that build limbs? Is this stuff active in building the skeleton of fish fins? Or are hands genetically completely different from fish fins? We saw an inner fish in the anatomy of our arms and hands. What about the DNA that builds it?
Enter Randy Dahn with his mermaid’s purses.
GIVING SHARKS A HAND
Randy Dahn entered my laboratory with a simple but very elegant idea: treat skate embryos just the way Cliff Tabin treated chicken eggs. Randy’s goal was to perform all the experiments on skates that chicken biologists had performed on chicken eggs, from Saunders and Zwilling’s tissue surgeries all the way to Cliff Tabin’s gene experiments. Skates develop in an egg with a kind of shell and a yolk. Skates even have big embryos, just as chickens do. Because of these convenient facts, we could apply to skates many of the genetic and experimental tools people had developed to understand chickens.
What could we learn by comparing the development of a shark fin to that of a chicken leg?
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