Fish With Creepy Curved Backbones Could Help Explain Scoliosis
In her lab at Princeton, Rebecca Burdine keeps a number of zebrafish with odd mutations. One of the most striking is curly, a mutation so severe it bends the fishs spine into a permanent C. It looks like an extreme case of scoliosis—a sideways curvature of the spine—most common in teenage girls.
Burdine, a developmental biologist, was studying congenital heart defects, not scoliosis, when she asked an undergraduate in her lab to grow curly zebrafish. It did not go well. She would say things to me like, I dont have mutants today, and Id say, But that makes no sense, recalls Burdine. It turned out something else was odd about the curly mutation: It was temperature sensitive. The warmer the water, the more fish grew curved spines. We didnt realize until later that she put them at different temperatures depending on her class schedule, says Burdine.
Ten years later, that accidental discovery has enabled a study, published in Science, that adds evidence to an intriguing new genetic cause for scoliosis. Its related, actually, to the congenital heart defects that Burdine was originally studying. What ties the two problems together are cilia, slender hair-like structures that project from cells.
Its easy to take for granted that our spines grow straight, our hearts on the left, and our limbs in pairs. But it actually takes incredible coordination. Every cell needs to know where it is so that, for example, the cells in your feet dont grow into an eyeball. In adeveloping embryo, cilia consistently beat fluid in a single direction that becomes left, so the heart grows on the left side of the body.
Cilia inside the spine also move cerebrospinal fluid, bathingthe spinal cord and brain. The spine spends a lot of time trying to sense whats going on in other parts of the body, says Burdine. Disrupt the regularflow of that cerebrospinal fluid—in the case of a tumor that blocks the fluid or defective cilia that can’t beat properly—and the spine begins to curve.
Burdine and her colleagues figured out that their curly zebrafish had defective cilia. To prove that defective cilia then led to curved spines, they made use of the curly mutations temperature-sensitive quirk. The team raised curly zebrafish at a cool temperature for 19 days and transferred them to warmer tanks until the fishs spines began to curve. Staying in warmer tanks made their spines more and more curved. Putting them back in the cool tank stopped it from getting worse.
The team checked out four other cilia-related mutations, and found they also caused the zebrafishs spine to curve. Last year, ateam in Canada and France found a different mutation in families with unusually high rates of scoliosis that affected cilia. When that team put theirmutation into zebrafish, it also caused the spine to deform. There is no one gene, one scoliosis, says Florina Moldovan, a spinal deformities researcher atthe CHU Sainte-Justine,who worked on that study.But together, these cilia mutationsmight explain some of the scoliosis cases doctors currently term idiopathic, official medical jargon for we have no idea why this happens.
Scientists still have to learnhow exactly the spine senses cerebrospinal fluid flow.Having the zebrafish as a good model for scoliosis is a huge step, though. Mice, a more common lab animal,aren’t good for studying scoliosis because they walk on all four feet, which stabilizes the spine. No ones reported much scoliosis in mice, says Christina Gurnett, a neurologistat Washington University in St. Louis. So giving mice scoliosis means taking pretty drastic measures, like amputating two legs to force them on their hind feet.
Other mysteries, like why scoliosis mostly afflicts teenage girls, still remain. With scoliosis, were not in the dark ages, but were catching up to a lot of other disorders, says Gurnett. Defective cilia may explain only some cases of scoliosis, but the theory is at least chipping away at the maddening label of idiopathic.
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