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.
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.