Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study of zebra fish mouth formation may speak to Fraser syndrome hearing loss

01.08.2012
Using mutant zebra fish, researchers studying the earliest formation of cartilage of the mouth believe they may have gotten a look at a mechanism involved in a genetic defect linked to Fraser syndrome deafness in humans.

Reporting in the Aug. 1 issue of the journal Development, they identify a potential developmental pathway worthy of more scrutiny in future research into Fraser syndrome, a many-faceted and rare recessive genetic disease.

In humans, a mutation in the gene FRAS1, which plays a role in skin epithelial formation during early development, has been linked to Fraser syndrome. A comparable version of the gene, fras1, in zebra fish is required for stable skeletal formation.

In the study -- done at the University of Oregon's Institute of Neuroscience -- researchers modeled craniofacial symptoms related to hearing loss in Fraser syndrome using mutant zebra fish, focusing on an endodermal pouch (known as p1), which in humans forms the Eustachian tube.

Using tissue labeling and time-lapse microscopy, the research team found "a previously unrecorded, late-forming portion of the first pharyngeal pouch in the zebra fish," said lead author Jared Coffin Talbot, now a postdoctoral researcher at Ohio State University. He earned his doctorate from the UO in 2011.

The newly seen component, researchers wrote, is a fras1-dependent "endodermal outpocket" -- referred to in the paper as a late-p1. "If this homology can be taken as a guide, then endodermal pouching defects might underlie some ear defects in Fraser patients," they concluded.

"In fras1-mutant fish, some skeletal elements near late-p1 do not form properly during this time period," Talbot said. "However, after this time period, two other skeletal elements that would have normally been separated by late-p1 fuse together in fras1 mutants that lack late-p1. We propose that in normal development late-p1 holds apart skeletal elements found fused in fras1 mutants."

To test that idea, the researchers -- in the lab of Charles B. Kimmel, professor emeritus of biology -- added healthy epithelia tissue from wild-type zebra fish, into fras1-mutant embryos. Doing so allowed for normal facial development in the mutants.

"To my knowledge, the connection between skeletal development and Fraser syndrome deafness has not yet been made in mammals," Talbot said. "The literature has been largely mute as to why skeletal defects are found in fras1 mutants; this is what made it an interesting topic to study, but it does make a direct zebrafish-human connection more difficult to make. We believe that the middle ear and Eustachian tube are the homologous structures to what we're studying in zebra fish."

Fraser syndrome is a poorly understood disorder that can affect multiple parts of the body, but the majority of cases involve the eyes. Canadian geneticist C.R. Fraser described the disease in 1962. The FRAS1 gene previously had been identified as an adhesive and signaling molecule in epithelial tissues. The new paper shows the gene also acts in epithelia to sculpt skeletal shape.

"Specifically, we learned that zebrafish fras1 acts in tissues homologous to the human ear canal to sculpt tissues homologous to the human middle ear," Talbot said. "To our knowledge, the shape of middle ear bones has not been studied in Fraser syndrome patients, nor has the Eustachian tube. We suggest that these tissues in human Fraser patients may prove highly fruitful."

Co-author John Postlethwait, a UO biologist, says his students often are intrigued when he shows them the similarities in the development of fish gills and their own Eustachian tube. "They know about what happens to their ears when they go up in an airplane, but are surprised at the evolutionary development of that ear-popping sensation," he said.

Another part of the new study also may provide insights into the many other faces of Fraser syndrome: partial webbing of fingers or toes; kidney abnormalities; genital malformations; and complete fusion of the eyelids.

"We carefully controlled for genetic and environmental factors by comparing the left and right sides of inbred zebrafish fras1 mutants raised in petri dishes," Talbot said. "When we did this, we found a remarkable degree of variation in skeletal defects. Our results appear to support the hypothesis that the degree of Fraser symptoms is to some extent determined by chance."

"These findings open a new window on the underlying mechanisms of this rare disorder," said Kimberly Andrews Espy, vice president for research and innovation. "Basic research in genetics at the UO using zebra fish as a tool reveals the fundamental dynamic processes that undergird development and helps to explain how it goes awry in medical conditions."

Co-authors with Talbot, Kimmel and Postlethwait are: former UO doctoral student Macie B. Walker, now at the University of Colorado Denver; Thomas J. Carney of the Institute of Molecular and Cell Biology in Singapore; Matthias Hammerschmidt of the University of Cologne in Germany; undergraduate UO student Tyler R. Huycke, now a technician in Kimmel's lab; Yi-Lin Yan and Ruth A. BreMiller, who work in Postlethwait's lab; high school intern Linda Gai; and April DeLauier, a postdoctoral researcher in the UO Institute of Neuroscience.

The National Institutes of Health supported the research (grants R01DE013834, U01DE020076, P01HD022486, T32HD007348 and T32GM007413). Hammerschmidt was supported by a grant from the German Research Foundation.

About the University of Oregon

The University of Oregon is among the 108 institutions chosen from 4,633 U.S. universities for top-tier designation of "Very High Research Activity" in the 2010 Carnegie Classification of Institutions of Higher Education. The UO also is one of two Pacific Northwest members of the Association of American Universities.

Sources: Jared Coffin Talbot, postdoctoral researcher, Ohio State University, 614-292-8084, talbot.39@osu.edu; John H. Postlethwait, professor of biology, UO, 541-346-4538, jpostle@uoregon.edu

Links:

UO Institute of Neuroscience: http://www.neuro.uoregon.edu/

About Charles Kimmel: http://www.neuro.uoregon.edu/ionmain/htdocs/faculty/kimmel.html

About John Postlethwait: http://uoneuro.uoregon.edu/ionmain/htdocs/faculty/postlethwait.html

Follow UO Science on Facebook: http://www.facebook.com/UniversityOfOregonScience

Jim Barlow | EurekAlert!
Further information:
http://www.uoregon.edu

More articles from Life Sciences:

nachricht O2 stable hydrogenases for applications
23.07.2018 | Max-Planck-Institut für Chemische Energiekonversion

nachricht Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Future electronic components to be printed like newspapers

A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.

The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

The Maturation Pattern of the Hippocampus Drives Human Memory Deve

23.07.2018 | Science Education

FAU researchers identify Parkinson's disease as a possible autoimmune disease

23.07.2018 | Health and Medicine

O2 stable hydrogenases for applications

23.07.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>