A study of zebrafish conducted by researchers from Princeton University and the University of Toronto, Canada, suggests that irregular fluid flow through the spinal column brought on by gene mutations is linked to adolescent idiopathic scoliosis (AIS) in humans. Found in zebrafish and humans, the mutated genes damage the motile cilia, tiny hair-like projections that line the spinal canal and help move the fluid, and lead to a curvature of the spine. By repairing the mutated cilia genes, the research team found that cerebrospinal fluid flow was restored and could prevent spinal curves from developing. If translatable to humans, the study could lead to a nonsurgical approach for treating AIS.
In the zebrafish’s brain regions known as ventricles, which sit at the top of the spinal cord, damaged motile cilia were sparse and malformed and the fish developed hydrocephalus, which is associated with loss of cilia function. Using fluorescent dyes to track the flow of cerebrospinal fluid through the ventricles, the researchers saw that the flow was irregular and slower than normal. The team found that the damage to motile cilia function occurs and leads to the onset of scoliosis during adolescence for zebrafish, a period of rapid growth. They also tested other motile cilia gene mutations to see whether they disrupt cerebrospinal fluid flow and cause spine curvature.
“This is the first hint of a biological mechanism for idiopathic scoliosis,” said Rebecca Burdine, PhD, associate professor of molecular biology at Princeton, and a senior author of the study. “We hope this research will open up new areas of inquiry as to how the disruptions to normal cerebrospinal fluid flow can lead to spinal curvature.”
“Traditionally, theories regarding the biology behind idiopathic scoliosis have revolved around defects in the bone, cartilage, or neuromuscular activity,” said senior author Brian Ciruna, PhD, an associate professor of molecular genetics at the University of Toronto and a senior scientist at the Hospital for Sick Children, Toronto. “The finding that defects in cerebrospinal fluid flow may be contributing to scoliosis came as a surprise. It is not a theory that had been put out there previously.”
The next step will be to understand the mechanisms by which disrupted cerebrospinal fluid flow causes the spine to curve, Burdine said. “Now that we can study idiopathic scoliosis in zebrafish, we can begin to identify molecular pathways that are involved in spine curvature, and hopefully, find therapeutic targets to address this condition,” she said.
The study was published June 10 in Science.
Editor’s note: This story was adapted from materials provided by Princeton University.