In the latest episode of Genetics Unzipped, supported by the Institute of Genetics and Cancer at the University of Edinburgh, presenter Dr Kat Arney sits down with Professor Bob Hill to take a look at the story of their favourite gene (we’ve all got one, right?). From six-toed Hemingway cats to cyclops lambs – and, of course, its fabulous name – the Sonic Hedgehog gene has a fascinating history, as well as a whole bunch of interesting science behind it.
“The original six toed cat was a gift to Ernest Hemingway by an old sea captain apparently,” says Bob. “Around Hemingway’s house is a group of about 50 or 60 cats – about half of those have extra toes on their front paws, those are the Hemingway cats.”
Bob and his team discovered that a tiny genetic change in a control switch that turns the Sonic Hedgehog gene on at the right time and place during limb development is responsible for giving these cats their extra toe. And it’s the same kind of change seen in humans and other animals with bonus digits.
Sonic Hedgehog is much more than just a ‘toe’ gene. It’s involved in patterning many different tissues and organs during development and is found in all vertebrates ranging from fish to birds to humans. More significant changes in Sonic Hedgehog have more serious consequences.
“It causes a condition called holoprosencephaly that affects predominantly the face and the head and the brain,” Bob says. “And because Sonic Hedgehog is expressed along the midline of most of these organ systems, what happens is the midline is essentially missing and it brings all those structures laterally closer together.”
As Bob explains, it was the discovery of this condition, holoprosencephaly, in a large number of lambs born to sheep grazing in a field populated by corn lilies (which produce a chemical called cyclopamine) that led to the development of Sonic Hedgehog inhibitors for treating childhood brain tumour and basal skin carcinomas.
And the name?
The Hedgehog gene was originally described in a very large genetic screen done in the fruit fly Drosophila melanogaster as a mutation that made fly embryos look rounded and bristly, like a hedgehog.
Once the Hedgehog gene had been found in fruit flies, the hunt was on to see if it was in mammals too. It turns out that mice have three versions of the hedgehog gene. One became known as Desert Hedgehog, another was dubbed Indian Hedgehog. The third got a more up to date name.
“At about the same time [the gene was discovered], this new computer game, Sonic the Hedgehog had just come out. And so they named it Sonic Hedgehog based on this new computer game.”
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Genetics Unzipped is the podcast from the UK Genetics Society, presented by award-winning science communicator Dr Kat Arney and produced by First Create the Media. Follow Genetics Unzipped on Twitter @geneticsunzip, and the Genetics Society at @GenSocUK
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