MEMPHIS, Tenn., July 15 /PRNewswire-USNewswire/ -- The molecular machinery that helps brain cells migrate to their correct place in the developing brain has been identified by scientists at St. Jude Children's Research Hospital. The finding offers new insight into the forces that drive brain organization in developing fetuses and children during their first years. Disruption of this brain-patterning machinery can cause epilepsy and mental retardation and understanding its function could give new insight into such disorders.
In the experiments, the researchers sought to understand the biological machinery powering a process called glial-guided neuronal migration. Glial cells in the brain support and guide neurons, which make up the brain's wiring. During brain development, neurons are born in germinal zones at some distance from where they must ultimately land in order to form brain structures and integrate into the brain's circuitry.
The researchers used a technique of microscopic time-lapse imaging to establish that Myosin II and actin made up the machinery of neuronal migration. Working with cultures of migrating neurons, the investigators used fluorescent dyes to label Myosin II and actin proteins, as well as key cell structures. The scientists then illuminated the cultures with rapid-fire pulses of laser light measured in thousandths of a second, taking an image with each flash. The result was a series of micromovies that revealed how the Myosin II and actin proteins and cell structures behaved during migration.
"No one had actually looked in living cells to see the configuration of actin in migrating neurons to show how it positions the machinery that will eventually elicit movement of the cell," Solecki said. "We also found that contraction of Myosin II in the leading portion of a neuron powers movement."
"Our time-lapse microscopy could image hundreds of cells in a single afternoon, but analyzing that mass of data by hand would have taken months," Solecki said. "However, the automated analysis enabled those data to be analyzed in a matter of hours. Also, the automated analysis was free of the kind of natural bias that can occur when humans analyze such images."
Basic understanding of the migration machinery could have important clinical implications.
Other authors of the paper are Niraj Trivedi (St. Jude); and Eve-Ellen Govek and Mary Hatten (The Rockefeller University, New York). The research was supported in part by the March of Dimes, the National Institutes of Health, a Cancer Center Support Grant and ALSAC.
St. Jude Children's Research Hospital