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Birth of Glial Cells RevealedThe function of glial cells, which together with neurons make up the central nervous system, is poorly understood, though they seem to play a supporting role to neurons. How glial cells come into existence at all is even more of a mystery. Using the rat eye as a model, a study appearing in the May Neuron brings this issue into focus.
A glial cell is formed in a rat retina by the overexpression of rax. The rax protein is labeled with a green fluorescent tag that lights up the cell. The retina contains one type of glial cell and six neuronal cell types that are born in a distinct order. Although the glial cells are some of the last to form, all of the cells in the retina are derived from a common progenitor cell. Former HMS research fellow Takahisa Furukawa and clinical fellow Siddhartha Mukherjee, first authors of the study from the lab of Howard Hughes investigator and HMS professor of genetics Constance Cepko, identified the genes that tell the progenitor cell to become a glial cell. The researchers identified three genes that were expressed in glia to a much greater extent than in neurons in the eyes of nine-day-old rats. The individual genes, rax, Hes1, and notch1, were then introduced into the eyes of newborn rats through injection of a retrovirus. The retroviruses contained the genes fused to green fluorescent protein that allowed the fate of the cells and their genes to be easily visualized. The forced overproduction of any of the proteins encoded by the genes caused the retinal progenitor cells to become glial cells. This study supports the idea that cells of the central nervous system arise from a common progenitor. In fact, as more glial cells were born, a marked lack of neuron formation was seen. This all-or-nothing control of cell fate appears to rely on a single gene, rax, which then activates the genes Hes1 and notch1. —Rebecca Bryant Job Stress: An Occupational Hazard for WomenA new study supports what many women have long suspected: a stressful job can be hazardous to your health. In a four-year survey tracking 21,290 women who were part of the Nurses' Health Study, those with demanding jobs that provided little autonomy or social support reported the steepest declines in their health. School of Public Health researchers Yawen Cheng, a former research fellow; Ichiro Kawachi, associate professor of health and social behavior; Graham Colditz, professor of epidemiology; and colleagues announced the findings in the May 27 British Medical Journal. While previous studies have implicated job strain in conditions such as hypertension, cardiovascular disease, and depression, this study included qualitative questions about vitality and social functioning. Women with jobs that enabled them to have a say in their own schedules were healthiest, and they maintained their health over the four-year study. In contrast, women who said they had too little time to do too much work and had to follow strict orders had the worst health. They also deteriorated the most. "This study shows that job strain also has broader health effects," says Kawachi. "And those effects get worse as the job strain continues." The research suggests employers could create more cooperative workplaces while actually helping their bottom line. "If workers are able to participate in decision making and have some flexibility and control over their jobs, then employers would be rewarded with fewer employee absences for health and even lower insurance rates," Kawachi says. —Maggie McKee Message from the Heart Affects Outside Vessel GrowthWhat initially began as a research project on blood cell differentiation has led to new insight into the development of the heart and coronary blood vessels. In a paper published in the June 23 Cell, a team led by Stuart Orkin, a Howard Hughes investigator and the Leland Fikes professor of pediatric medicine at Children's Hospital, and Sergei Tevosian, Howard Hughes research fellow in pediatrics, suggests that the embryonic heart muscle tells its surrounding tissue to form the blood vessels needed to survive. Orkin's lab has been studying the GATA family of transcription factors as well as GATA partner proteins FOG and FOG-2. The research initially focused on how these factors regulate gene expression in blood cells. But because FOG-2 is highly expressed in the heart and brain, studying the function of the protein led the team from blood into new territories of tissue. In the FOG-2–deficient knockout mice they generated, Orkin's team expected to find abnormalities in the heart that could be linked to genes thought to be regulated by FOG-2. But although the hearts had abnormalities resembling a congenital heart defect in children called the tetralogy of Fallot, there were no striking changes in gene expression that could be attributed to potential FOG-2 targets. In fact, the most devastating effect they observed was a complete failure to form the coronary vessels that feed the heart with blood. This is surprising because coronary vessels do not arise from the heart muscle itself, but from its surrounding epithelial layer. Why did a protein localized in the heart have its major effects on activity outside the heart? In order to determine where FOG-2 was needed for vascular development, the team generated transgenic mice that expressed FOG-2 only in the heart muscle and found that these mice were able to form coronary blood vessels. This evidence suggests that the heart muscle communicates with its surrounding tissue, signaling the formation of vessels to nourish it. The nature of this signal is unknown, but FOG-2 is somehow needed for it to function. As a newcomer to this area of developmental biology, Orkin says, "I think it's surprising that there is relatively little known about the molecular induction of heart vessel development." |
