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 Researchers develop eco-friendly, 4-in-1 catalyst
25.04.2017 | Brown University

nachricht Transfecting cells gently – the LZH presents a GNOME prototype at the Labvolution 2017
25.04.2017 | Laser Zentrum Hannover e.V.

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

NASA's Fermi catches gamma-ray flashes from tropical storms

25.04.2017 | Physics and Astronomy

Researchers invent process to make sustainable rubber, plastics

25.04.2017 | Materials Sciences

Transfecting cells gently – the LZH presents a GNOME prototype at the Labvolution 2017

25.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>