Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Vax and Pax: Taking turns to build an eye

17.10.2006
Opposing ball clubs don't take the field at the same time, and neither do teams of proteins responsible for creating the eye. While one team builds the retina, in adjacent cellular turf the opponents are busy constructing the cord that carries visual signals to the brain. And these guys aren't supposed to mingle.

That's why researchers at the Salk Institute for Biological Studies were surprised to find the respective team captains--Vax2, a protein that along with Vax1 builds the optic nerve cord, and Pax6, a protein that drives retinal fate--playing on the same field. That puzzle is explained in a forthcoming paper in Genes and Development.

Earlier studies from the laboratory of Greg Lemke, Ph.D., professor in Salk's Molecular Neurobiology Laboratory, had shown that Vax2 antagonized Pax6. "We knew that Vax1 and 2 acted together to inactivate Pax6. That's how you get an optic nerve--by preventing it from becoming a retina," explains Lemke. The only problem was that later on both Vax2 and Pax6 were co-expressed in the same cells. "If Vax2 was repressing Pax6 this seemed inconsistent," he says.

Both proteins bind DNA and function in a cell's nucleus to switch genes on and off. Pax6 regulates the development of the retina, while Vax2 ensures that the optic nerve gets built. Finding both proteins in the same nucleus would make about as much sense as having runners for the Giants and the Dodgers on base at the same time.

... more about:
»Nucleus »Pax6 »Retina »Vax2 »optic nerve

Analyzing eye development in both mouse and chick tissues, Lemke and former postdoctoral fellow Jin Woo Kim, Ph.D., solved the mystery. Stina Mui, a former graduate student in the Lemke lab had originally observed Vax2 in the cytoplasm of cultured cell lines and Kim had taken on the task of figuring out why. He showed that Vax2 protein is indeed expressed in the same retinal cells as Pax6, but that Vax2 shuttles in and out of the nucleus in response to a signaling molecule known as Sonic hedgehog.

"Vax2 only entered the nucleus when its biological activity was needed," says Kim. Once its job was done, Vax2 was apparently booted out of the nucleus into the cytoplasm where it remained in cellular time-out.

Kim and Lemke found that Vax2 shuttling was controlled by a chemical modification known as phosphorylation. Phosphorylation benched Vax2 in the cytoplasm, where it took a breather while Pax6 took over to form the retina. Kim then made a dramatic discovery. When he engineered a Vax2 protein that could not be phosphorylated--putting Pax6 permanently out of commission--and forced that protein into chick retinal precursor cells, the chicks had no eye.

"What you had was a chicken with just a big optic nerve," says Lemke, noting with satisfaction that this was exactly the opposite outcome his group had observed when they genetically eliminated Vax2 and Vax1 genes from mice. "In that case you had no optic nerve but a giant eye. This basically says that you really have to get this protein out of the nucleus--if you keep it there you get no retina at all."

But why doesn't mother nature simply dispose of Vax2 when she's finished with it? Most likely because it's recycled for use again later in development. Explains Lemke, "This is a mechanism for pushing Vax2 aside--so it can't do any damage by repressing Pax6--but keeping it close by so it can be quickly activated when it is needed again later on."

"One consequence of this work is that we learn things ultimately important for medicine," he continues. "The Sonic hedgehog pathway plays an important role during embryogenesis and also in the development of a series of cancers. Understanding the pathway is directly relevant to a whole spectrum of human diseases."

Kim, who is now an assistant professor at Korea Advanced Institute of Science and Technology (KAIST) in Daejeon, South Korea, will continue collaborating with the Lemke lab by engineering a so-called "knock-in" mouse expressing the nonphosphorylatable protein in the normal developmental timeframe. The prediction is that, like the chicks, that mouse should have big problems making an eye. Stay tuned.

Gina Kirchweger | EurekAlert!
Further information:
http://www.salk.edu

Further reports about: Nucleus Pax6 Retina Vax2 optic nerve

More articles from Life Sciences:

nachricht How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH

nachricht A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Quantum thermometer or optical refrigerator?

23.06.2017 | Physics and Astronomy

A 100-year-old physics problem has been solved at EPFL

23.06.2017 | Physics and Astronomy

Equipping form with function

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>