image: This photo is of the sighted, surface-dwelling fish related to the ancient, eyeless Astyanax mexicanus. view more
Credit: Jay Yocis
A $1.92 million, five-year R01 Award from the National Institutes of Health will support University of Cincinnati research into the genetic aspects of craniofacial asymmetries that could address a wide spectrum of human conditions, from non-syndromic cleft palate to hemifacial microsomia - conditions that can impair breathing or lead to emotional suffering from distorted appearance. In addition, UC biology researcher Joshua Gross, an assistant professor of biological sciences, was awarded $519,343 from the National Science Foundation to explore the genetic explanation for pigmentation loss in cave animals, which could also hold links to pigmentation changes in humans. Both awards get underway in March.
The researchers are searching for genetic hints by examining a species of eyeless, cave-dwelling fish, Astyanax mexicanus - which has lived in the pitch-black caves of the Sierra de El Abra region of Mexico for millions of years. These fish can be compared with the closely related sighted surface-dwelling fish that are found in Mexico, Texas and New Mexico. Previous research suggests that genetic mutations leading to craniofacial distortions in the cavefish may be similar to human facial abnormalities that often result in painful, corrective surgeries as early as infancy. The closely-related surface-dwelling fish do not have these facial abnormalities.
The funding will support genome-wide mapping which will allow researchers to zero in on the precise region of the genome - specific genes as well as mutations within genes - that will explain these facial asymmetries.
The research project will examine these three levels:
- First, the project will explore if asymmetric transcriptional signaling across the left-right axis of the cavefish during embryonic development accompanies and impacts asymmetric bone fragmentation.
- Secondly, researchers will examine specific genes that may be causing asymetry. "We want to understand if the right side of the face is different from the left side of the face within an individual and if so, we want to know why," says Gross. "Nowadays, you can look at the precise expression level of every gene in an entire genome. We want to do that in the cavefish to explore what is happening on the right side that is different from the left side."
- Lastly, the researchers will examine embryonic cells called the neural crest, which migrate very early in development. "Think of them like a big mass of ping pong balls," explains Gross. "Some scatter to become bone, others become cartilage, others affect pigmentation, neuronal cells and so on. We want to gain more understanding around the cells that become bone and cartilage, compare them between the cavefish and the surface fish, and see if that might explain why the cavefish are asymmetric."
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Gross says the project began with an appreciation for the fact that symmetry is an important component of human perceptions of facial attractiveness. "This trait evolves under intense sexual selection as a signal of robust physical health and genetic quality in potential mates," states the research proposal. "Think of couples like Brad Pitt and Angelina Jolie, who are admired worldwide for their physical features," says Gross. "The logical flow of this is that facial attractiveness is believed to be an indication of strong genetic composition - a strong mate who will provide for your offspring - and so indirectly there may have been evolutionary pressures acting on our ancestors to maintain facial symmetry in humans.
"Cavefish have naturally lost their eyes over the course of evolution," continues Gross. "The fish can't see one another anymore, so the left and right sides of their faces become uncoupled and begin to exhibit random asymmetries. One of our most surprising discoveries is that there's actually a genetic basis for that asymmetry. Some changes in the genome have resulted in one side of the face developing differently from the other side of the face. Because this process occurs so often, cavefish are a powerful natural model system for learning about this fundamental biological phenomenon of craniofacial symmetry."
The UC researchers have previously found two genes in the cavefish that are closely tied to non-syndromic cleft palate in humans.
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About the NIH R01 Grant
The prestigious National Institutes of Health Research Project Grant (R01) is the original and historically oldest grant mechanism used by the NIH. The R01 provides support for health-related research and development based on the mission of the NIH.
Award from the National Science Foundation Launches Additional Line of Genetic Research in March
A new three-year, $519,343 NSF award to Gross' research team will explore an additional avenue of genetic research involving the blind Mexican cavefish which may also help increase understanding of pigmentation changes in humans. Previous UC research found that the gene that causes red hair and pale skin in humans was the same gene that caused reduced pigmentation in cavefish compared to the surface-dwelling species.
The NSF grant will also support plans for educational outreach programs involving Gross' biology research lab and the development of education programs for preschool children, the recruitment of female STEM researchers through UC's Women in Science and Engineering (WISE) Fellowship Program, high school summer research fellowships and public education outreach programs.
The Research Team
Bethany Stahl, doctoral candidate - Stahl is credited with adapting a genome editing technique that can test the function of specific genes by injecting fish eggs just after fertilization, a technique that cannot be done in humans, yet findings may identify genes in other genetic disorders. Gross says Stahl has contributed to significant advancements internationally in cavefish genome research.
Brian Carlson, doctoral student - Carlson was key in developing the linkage maps tracing genetic markers and the relationship they have to one another on the physical chromosome. These maps can be used for genetic analyses, facilitate comparisons with other species and also will help identify the genes causing cave-associated traits.
Amanda Powers, doctoral student - Powers is using hi-tech software to image and measure "virtual" fish skulls at different stages of development, searching for fragmentation as well as when the asymmetries are occurring during the development of bone and cartilage.