HMS Researchers Find First Link Between Bone Growth Gene and Cognitive Functioning

Neurobiologists at Harvard Medical School have discovered the first link between a bone growth gene and cognitive functioning in humans and nonhuman primates.

The findings, from a study released earlier in November, are linked to understanding human evolution, the development of the human brain, and cognitive diseases, according to co-first authors on the study Bulent Ataman and Gabriella L. Boulting, who are research fellows in neurobiology at the Medical School.

Ataman started the study in 2011, building off research that had been done for many years with senior investigator Michael E. Greenberg, a professor of neurobiology and the current chair of the Medical School’s neurobiology department. The study indicates that osteocrin is the first gene to undergo genetic repurposing in the human brain. The role that osteocrin plays in human brain development distinguishes the human brain from that of what is typically studied in mice, according to the researchers.

“It’s important because it gives us insight into how the brain has evolved over time,” Greenberg said. “This provides good evidence that it involves mutations within regulatory reasons called enhancers. It has this capacity in a very basic way to start a new research area that allows us to understand the special features of human brain development that occur in response to sensory input or experience. Basically, if you want to understand human brain function, you can’t study it just in the mouse.”

Furthermore, the gene osteocrin has been linked to an intellectual disability, which leads the team to believe that it may be key in understanding cognitive dysfunction in humans, according to Greenberg.

Their research did not start with examining osteocrin directly, but rather understanding gene transcription and the response of human neurons to sensory experience, said the researchers, because the genomes of rodents and other animals cannot always accurately model cognitive brain disorders affecting humans.

Boulting said the original hypothesis was that there may be "fundamental differences between the way human neurons work and develop and integrate with each other" as compared to neurons used to model diseases in different organisms.

“We wanted to understand if those were readily detectable just by simply stimulating the human neurons and looking at which genes were being used in reaction to that stimulation and then comparing those genes with the same treatment of mouse neurons and rat neurons,” Boulting said.

The team intends to use their findings to examine how osteocrin affects the nervous system from “beginning to end,” according to Ataman.

“We have reason to think that there are others and one goal for the future is to identify other genes that maybe function like osteocrin but in a somewhat different way, selectively in a primate or maybe specifically human brain and figure out what they do,” Greenberg said.