Tiny Fish Reveal new clues to Origins of Scoliosis

Credit: University of Oregon

Young adult zebrafish from wild-type and cfap298 mutant lines

Credit: University of Oregon

Daniel Grimes

Newswise — Scientists have discovered new clues to the genetic basis for scoliosis, an abnormal curvature of the spine.

Why this is important:

Scoliosis, a common, sometimes hereditary spinal condition, is a curvature of the spine that affects 2% to 3% of the population in the United States.
Researchers in the lab of biologist Dan Grimes have identified two tiny proteins that help keep the spine straight during key periods in development.
Zebrafish with mutations in these proteins end up with curved spines, mimicking what’s seen in people with scoliosis.
The team reported their findings December 1 in the journal eLife.
The research and follow-up studies could be used to inform scientists’ broader understanding of animal form and function, too.

How it works:

Humans’ bipedal posture puts pressure on the spine in a way that isn’t replicated by four-legged lab animals like mice and rats, so it’s been hard to study spinal curvature in the lab.
As a postdoctoral researcher, Grimes spotted zebrafish with curved spines, resulting from genetic mutations.
Grimes found that waving cilia—tiny hairs lining the spine—push cerebrospinal fluid along. The fluid movement through the spine was essential for keeping it straight.
Fish with mutations that disrupted the cilia (and thus the fluid movement) ended up with curved spines.
Zebrafish with mutations in two specific proteins end up with a curved spine, mimicking what’s seen in people with scoliosis, the team showed.
“If we mess with them during adolescence, we see big spine curves,” Grimes said. “That shows the pathway is really operational during these growth stages—just as we see in humans, when scoliosis typically onsets in teenagers.”

Next Steps:

Next, the team plans to study what happens further along this pathway, with the hopes of better understanding the root causes of scoliosis.
“One of the main interests in my lab is to understand how small molecular processes give rise to big anatomical shapes,” Grimes said. “This is a good model for that, because it's neurons, muscle, bone all coordinating together.”

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