hybrid cavefish skull
April 5, 2014

Possible Genetic Link Discovered Between Cavefish And Human Facial Asymmetries

redOrbit Staff & Wire Reports - Your Universe Online

A newly-identified genetic association with facial asymmetry in ancient cavefish could shed new light into mysteries surrounding conditions such as cleft palate or hemifacial microsomia in humans, according to research appearing in a recent edition of the peer-reviewed journal Genetics.

Joshua Gross, an assistant professor in the University of Cincinnati’s Department of Biological Sciences, and his colleagues compared the craniofacial features of the Astyanax mexicanus, an eyeless fish that has lived in the dark caves of Mexico’s Sierra de El Abra region for millions of years, with related fish living in Mexico, Texas and New Mexico.

The cavefish are said to be extremely sensitive to sound and vibration, and while they have no eyes, they do possess bony features in their eye regions that are similar to their sighted, surface-dwelling relatives. Those similarities allowed Gross and his fellow investigators to compare traits in both the cavefish and the surface-dwellers.

“The researchers are screening the genomes of every individual fish from a hybrid pedigree housed in their lab – looking for genes that may lead to variations in eye size or pigmentation,” Dawn Fuller of the University of Cincinnati explained in a statement. “In the cavefish, they discovered genetic markers on two separate chromosomes that are associated with extensive bone fragmentation on the right side of the skull.”

While there was also bone fragmentation discovered on the left side of the skull, no genetic links were uncovered when the researchers looked at the cranium’s left side. None of these craniofacial abnormalities were demonstrated by the sighted fish, and the researchers hope that by studying how genes behave differently on each side of the face, they will learn why so many craniofacial alterations only exist or are worse on one side of the human face.

Gross and his co-authors, doctoral students Amanda Krutzler and Brian Carlson, are getting closer to identifying the exact genes associated with the cranial abnormalities. There are indications that a pair of genes previously linked to cleft palate in humans – bone morphogenetic protein number four (BMP4) and transforming growth factor beta family member 3 (TGFB3) – could also play a role in the natural forms of bone asymmetry.

The study, which was supported by a grant from the National Institute of Dental and Craniofacial Research, comes in the wake of previous research which discovered that the gene that causes humans to have red hair and pale skin is the same one that causes surface fish to have more pigmentation than the albino-like cavefish.

The University of Cincinnati investigators cross-bred the cave fish with the surface-dwelling fish, then intercrossed the hybrid offspring. Some of the resulting fish appeared to have the lower pigmentation levels of the cavefish but had well-developed eyes, while others were darker in color but had smaller, less developed eyes.

“We can make progress towards understanding the genetic origin of several analogous human disorders by expanding the repertoire of model systems represented by lab mice, zebrafish and so forth,” Gross said.

“Many techniques and technologies have been developed in these powerful model systems, however they’re extremely inbred,” he added. “As a result, an inbred model system is not going to enable us to understand how and why craniofacial abnormalities evolve in nature. We can use the blind Pachón cave-dwelling fish to inform unresolved questions, such as how and why asymmetric craniofacial malformations occur in humans.”

Gross concluded that additional research that uses a higher quantity of cave-dwelling models will help the research team learn more about some of the longstanding issues in contemporary evolutionary and vertebrate biology.

He and his colleagues are using technology from the Imaging Research Center at Cincinnati Children’s Hospital Medical Center to perform micro-CT scans on over 200 related types of fish. They captured more than 1,000 X-ray images for each fish, and then combined those into a high-resolution skull model using software that allowed them to manipulate it in three dimensions and take measurements of any noteworthy features.