Researchers at the University of Oregon have made important discoveries into the genetics of scoliosis, an abnormal curvature of the spine.
UO biology professor Dan Grimes and his team of researchers have discovered two small proteins that play an important role in maintaining spinal alignment during critical stages of development. When these proteins are mutated in zebrafish, the fish develop deformed spines similar to those of people with scoliosis.
Research was published by the group on December 1 in the journal eLife. The laboratory where Dr. Grimes works is situated in the Department of Biology of the College of Arts and Sciences at the University of Oregon.
Idiopathic scoliosis is the form of the disorder that does not have a known cause, and it often appears in adolescents, often at a period of rapid growth. Still, there is a great deal about scoliosis that scientists don’t yet know.
It has been challenging to investigate spinal curvature in the lab because of the unique stresses placed on the spine by humans’ bipedal posture that are not experienced by four-legged lab animals such as mice and rats.
However, while working as a postdoctoral researcher, Grimes noticed zebrafish with curled spines. Grimes speculated that the thrusting motion of the fish through the water might be more analogous to the pressures experienced by the human spine.
Upon additional investigation, he discovered that cerebrospinal fluid is pushed forward by microscopic hairs called cilia that wave down the spine. Maintaining a straight back required constant, smooth movement along the spine. Fish whose mutations affected their cilia and, by extension, their ability to swim fluidly, developed spines that were curled.
The next logical step in the process is laid out in this recently published study. The group revealed that zebrafish with mutations in two different proteins developed a curved spine similar to that of people with scoliosis.
Spinal neurons produce the two small proteins. The cilia in the body’s spinal cord are responsible for turning on their production. The researchers hypothesize that once these proteins are released by the neurons, they bind to receptors in the muscles surrounding the spine, potentially altering the way in which these muscles support the spine.
At specific stages of development, the proteins appear to play an especially important role. Some of the studies involved fish that were particularly vulnerable to changes in temperature. They found that they could switch genes on and off at will by manipulating the tank’s water temperature.
Big spine curvature, Grimes explained, are the result of interference throughout the “adolescent” years. In humans, scoliosis often develops throughout adolescence, and this finding supports the idea that the route is active during this time of rapid growth.
The next step in the team’s quest to discover the root causes of scoliosis is to investigate what occurs farther along this pathway.
Graduate student Zoe Irons said that it is a kind of a mystery how the protein itself gets it to the receptor.
The results can also contribute to scientists’ overall knowledge of animal structure and function.
How small molecular processes give rise to huge anatomical structures is a topic of intense study at Grimes’s group. Since it involves coordinated activity from nerve cells, skeletal muscle, and bone, it serves as a useful analogy.
Elizabeth A Bearce, Zoe H Irons, Johnathan R O’Hara-Smith, Colin J Kuhns, Sophie I Fisher, William E Crow, Daniel T Grimes (2022) Urotensin II-related peptides, Urp1 and Urp2, control zebrafish spine morphology eLife 11:e83883. https://doi.org/10.7554/eLife.83883