Trigger for brain plasticity identified

Researchers have long sought a factor that can switch on the brain's ability to learn. Now, research led by Takao Hensch, PhD, of Children's Hospital Boston's FM Kirby Neurobiology Center and the Department of Neurology, has identified such a trigger. Called Otx2, it signals certain cells in the cortex (parvalbumin cells) to mature and initiate a critical period—a time window when the brain can readily rewire itself.

Surprisingly, the signal actually comes from the eye—but only after the eye has matured enough to provide good vision. Hensch speculates that other sensory organs may send similar signals to the brain as they mature, triggering critical periods for hearing, smell, etc.

Controlling the onset of plasticity could help in developmental disorders like autism, in which critical periods are thought to be mis-timed. "If the timing is off, the brain won't set up its circuits properly," says Hensch. Launching a critical period might also help people recover from stroke or brain injury, or learn languages or musical instruments as easily as young children, adds Hensch, who last fall won the highly competitive National Institutes of Health Director's Pioneer Award. He also speculates that Otx2 could be harnessed to carry drugs from the eye to the brain, envisioning eye drops for disorders like amblyopia (lazy eye). Sayaka Sugiyama, PhD, postdoctoral research fellow, was first author of the study, published in Cell on August 8.

Growing new blood vessels

A major challenge in tissue engineering has been the need to provide a blood supply to the implanted tissues and organs. Now, Juan Melero-Martin, PhD, research fellow in the Department of Surgery and the Vascular Biology Program, Joyce Bischoff, PhD, principal investigator in the Vascular Biology Program, and colleagues have successfully grown functioning human blood vessels in mice by implanting progenitor cells from human blood and bone marrow.

Seven days after cell injection, numerous vessels had formed in the mice, carrying visible red blood cells (left panel). The vessels contained a lining of endothelial cells (right panel, shown in red) and an outer layer of mesenchymal progenitor cells (green). (Cell nuclei appear in blue.) Courtesy Joyce Bischoff, PhD.

Within seven days, the cells had formed extensive networks of two-layered blood vessels, without the need for genetic manipulation to improve their growth (important since many growth-promoting genes are also activated in cancer). The vessels continued to transport blood throughout the month-long study.

Getting new vessels to form—by injecting progenitor cells in the right locations—may also help patients with heart attacks, atherosclerosis and other conditions where tissues are starved for blood. "What we're most interested in right now is speeding up the vascularization," Bischoff says. "We'd like to see good vasculature within 24 or 48 hours. If you have ischemic tissue, it's dying tissue, so the faster you can establish blood flow the better." The study appeared in the July issue of Circulation Research.

Cancer: getting the big picture

Cancer researchers devote much attention to the role of individual genes. But a group in Children's Informatics Program (CHIP) has been studying cancer in a more holistic way, comparing the complete gene activity profiles of a broad range of cancers to gene activity patterns seen during embryonic development. Three major cancer categories emerged from this analysis, offering some surprising insights.

One group of cancers has gene activity patterns¬Ýthat are proliferative, stem-cell-like and similar to those of early development, says Kamila Naxerova, the study's first author and a graduate student working with CHIP director Isaac Kohane, MD, PhD. These cancers tend to grow aggressively. The second group, with more indolent cancers, expresses many genes linked to inflammation, a pattern seen during late embryonic development. The third group falls somewhere in the middle.

Grouping cancers this way may help predict prognosis, and could even lead to new therapeutic strategies. For example, both the lung cancer adenocarcinoma and Wilm's tumor, a pediatric kidney cancer, landed in the early developmental group. "It's not what I would have expected, since these cancers arise under very different circumstances and are associated with different genomic alterations," says Naxerova.

In other words, as unlikely as it seems, drugs effective against lung cancer might potentially be used to treat kidney tumors in children. The study appeared in the July issue of Genome Biology.