In a small fruit fly lab on the third floor of Fleischmann Agricultural building at the University of Nevada, Reno, exciting discoveries are being made. Winding around the maze of workstations and equipment, the entire space is teeming with new ideas. Jars of incubating flies sit in neat rows in a large refrigerator against the wall, students study specimen under elaborate microscopes, others cleans instruments to be used for the next day. In the back corner of the lab, engrossed in images of mutations in the flies sits Dr. Thomas Kidd, an associate professor in the university’s biology department.
Dr. Kidd and a team of neuroscientists in the biology department at UNR have recently identified a new genetic mechanism in a split-brain fruit fly that may give valuable insights into the cause of autism. This gene, called PRRG4, is believed to be responsible for the disruption of brain pathways connecting the left and right sides of the brain.
Dr. Thomas Kidd has been working at UNR since 2003, teaching a variety of genetic and neuroscience classes while studying the wiring of the nervous system, and how nerves grow and navigate within the body.
Dr. Kidd begins describing his work with a picture of a neuron, or nerve cell. A cell body surrounded by spindly dendrites, operating in a similar way to antennas on an insect, sensing the surrounding environment. The cell body is connected to the axon, the passage in which messages from the cell body get passed on to other neurons, muscles or glands. This description only scratches the surface of the complex working unit of the brain, which has multiple functions.
Dr. Kidd and his lab focus on how neurons grow and navigate within the body by studying fruit flies. A fruit fly’s brain and nerve cords form using molecules that are surprisingly similar to those in humans. “Every gene we’ve ever found in the fly is usually doing the same thing as in humans,” said Kidd.
Over several years research of the fruit fly nervous system was conducted, leading to a surprising discovery. Kidd and his team found a mutant fruit fly that had no connections between the right and left side of its nervous system. Just like humans, a fruit fly relies on connections between the left and right side for coordinated, smooth movement and communication. These connections are found in six important places in the human body, the biggest being the corpus callosum, which joins the two hemispheres of the brain.
A normal corpus callosum looks like a ladder: with axons connecting two vertical pathways to the brain. The connection points are called commissures. The corpus callosum forms during pregnancy and subtle disruptions to the structure are associated with developing autism. In the mutant fruit fly, Kidd’s team found, there are almost no connections between the left and right side of the nervous system.
“This [fly] is absolutely amazing,” Kidd said while pointing to an image of the fly’s nerves. “It was the poster child for our study because it really has no left right connections. It’s like the ultimate split-brain patient.”
The mutant is called commmissureless, or comm, and after discovering this mutant, Kidd said he and his colleagues began work to identify the human equivalent of the comm gene.
“The comm gene was thought to be unique to insects but our work shows that it is not,” said Elizabeth Justice, a former postdoctoral neuroscience researcher in Kidd’s lab and lead author of the study, said to reporter Mike Wolterbeek.
“…[Scientists] have been looking for over 25 years, it was really well hidden,” said Kidd. After more than five years, they found it. The human gene is called PRRG4. It was stated in the study that reduction in PRRG4 levels alters connectivity patterns in the developing brain. Connectivity defects have been suggested as potentially underlying some cases of autism.
The study was published in the PLOS Genetics journal at the end of August, and since then has received a lot of attention, generating many ideas for futurestudies.
A perspective in response to the study was also published in PLOS Genetics due to its significance.
“Understanding the genetic mechanisms underlying the assembly of brain circuits is likely to be essential to the design of new diagnostic tools and therapeutic strategies for Autistic Spectrum Disorders,” Jimena Berni wrote in the perspective.
Dr. Kidd said he is excited by the potential discoveries that this gene will lead to, as further research is already being done on different specimen, testing the effects of the gene and how it changes left and right side neurological developments and connections, and whether it is present in different parts of the human brain.
The PRRG4 gene brings up new questions about the connectivity theory of autism which argues individuals have a more local connection in the expense of long range ones, therefore possess increased ability in some areas. The similarities between split brain patients and those with autism is also an area that is being studied.
“We know that brain wiring is altered in autism spectrum disorders and our own work has found similarities in the way visual information is integrated between the two brain hemispheres of split-brain patients and autistic individuals,” Hutsler said in an interview with Nevada Today. “It is therefore very plausible that PRRG4 will be found to play a part in the altered formation of the corpus callosum in individuals with autism.”
As research on the molecules continues within multiple laboratories on campus, Dr. Kidd and other professors are enthusiastic about the future discoveries to come.
Emily Fisher can be reached at firstname.lastname@example.org and on Twitter @NevadaSagebrush.