Under the microscope, it's hard to tell brain cells apart. But appearances can be deceiving. Scientists have found that, in fruit flies, a gene called Dscam comes in 38,000 flavors, enough to endow specific groups of neurons, even individual cells, with a unique identity.
Dscam, which stands for Down syndrome cell adhesion molecule, likely helps guide the developing connections between cells early in life. Like many genes, Dscam consists of protein-coding regions called exons interspersed with noncoding regions. Scientists have generally assumed that one gene codes for one protein. But parts of each of four exons in Dscam can become active separately, at different times--a process called alternative splicing. Each combination creates a different protein. In humans, Dscam plays a role in the developing heart, but the gene lacks the incredible variability seen in insects and so its exact role in setting up the nervous system is unclear.
Although immune system genes are able to mix and match their exons, researchers were initially surprised to find another gene in which so many combinations were possible, says study co-author Andrew Chess, a evolutionary developmental biologist at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts. To study the variations, Chess and his colleagues turned to DNA microarrays. When exposed to genetic material, the array reveals which genes are most active. By customizing the array, Chess and his colleagues could assess the activity of each Dscam variant.
The researchers exposed the microarray to genetic material belonging to fruit fly embryos, larvae of different stages, and adults. Different combinations of Dscam were active at different ages, they report this week online in Nature Genetics. There was even variety among individual neurons. Their analyses showed that each variant formed independently of the others and that the patterns of gene expression were somewhat random. The variability "is making each cell know it's different from its neighbor," says Chess.
"This is the first evidence for the possible presence of distinct Dscam molecules in individual [nerve] cells," says Tzumin Lee, a cell biologist at the University of Illinois, Urbana-Champaign. What's next, he adds, is to show "whether and how the presence of distinct Dscam molecules helps provide for the huge diversity and specificity in the central nervous system."