It’s rare to find a complete explanation for what causes a disease, but, in some fortunate cases, researchers can identify a gene that contributes to the progression of the disease. Chair of the Department of Genetics and Genome Sciences Dr. Anthony Wynshaw-Boris was the co-principal investigator in a study that pinpointed three genes whose absence can promote hydrocephalus.

Hydrocephalus is a condition caused by the build-up of cerebrospinal fluid in parts of the brain. It can harm a person’s motor skills, senses and reading abilities.

Normally, the brain floats in a liquid that protects, regulates and removes waste. In obstructive hydrocephalus, though, the excess fluid squeezes the brain, resulting in a number of problems.

Wynshaw-Boris found that the lack of three developmental genes, called the Dishevelled genes (DvI genes), changed the way cerebrospinal fluid moved in the brain by affecting the location of hair-like extensions on cells called cilia. When displaced, the cilia don’t move the fluid properly, resulting in build-up.

Wynshaw-Boris graduated from CWRU’s medical school with a medical and doctorate degree in 1987. He began work on this project while in California, where he found that, if the DvI genes in mice were removed before birth, the embryos would die.

He found that the absence of DvI genes changed cilia formation in gastrulation, a part of the mouse’s early development where cells begin moving to properly position themselves.

Normally, cilia form near the edge of the cell, where they can properly move the fluid. Instead, Wynshaw-Boris found that they were forming in parts of the cell where they couldn’t function properly.

He describes the misplaced genes as oars that aren’t properly positioned in water– they don’t move the water, or the boat.

He found that if one or two of the genes were allowed to remain intact, the mice were able to develop, but with abnormalities. This proved that each gene alone could impact cilia formation.

Wynshaw-Boris then decided to expand his research to see if the DvI gene’s effect on cilia was responsible for hydrocephalus. He used mice who had a few DvI genes left, who had grown into seemingly normal adults. However, through the study, he found that that was not the case.

“The fluid is outside the brain, but also inside the brain in areas called ventricles,” he said. “When we looked, we saw that the ventricles were enlarged.”

Wynshaw-Boris hopes to continue to study hydrocephalus to try to find a treatment for the rare disease. Using data from previous cases, he’s helped to diagnose hydrocephalus. He sequences blood samples and compares it to the patient’s parents, or uses stem cells from the patient’s skin to study abnormalities in the cell that could be altered by current drugs.

“Let’s say we sequence, we make [stem cells], we do the drug screening, if we have any success in any one of those areas it’s good for the patients,” he said. “Mostly if we find the gene and tell them this is causing your problem, that’s important.”