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The idea of self vs. nonself may sound more like an existential identity crisis than a question in cellular biology. But to Andrew Chess of the Whitehead Institute and MIT, the concept could offer information about how cells tell each other apart, a cellular self-awareness that ensures the correct wiring of neurons in the brain.
In research published in the March issue of the journal Nature Genetics, Chess and others in his lab examined the role a gene called Dscam plays in allowing neuron cells to distinguish themselves from one another. Dscam is a cell-adhesion molecule that helps to guide axons to their intended targets.
While the majority of genes produce at most just a handful of proteins, Dscam can generate some 38,016 different proteins in fruit flies, each having a slightly different structure and function. That quality alone would be enough to make the gene an interesting target of study. But Dscam made an attractive subject for other reasons as well.
"We knew Dscam was extremely complex, that it was expressed in neurons in the brain and that other cell adhesion molecules had been shown in other species to be important in how neurons connect to each other," said Chess, an associate professor of biology at MIT and a Whitehead associate member. "It made us think that studying Dscam may allow us to uncover some kind of new mechanism for how cells or groups of cells tell each other apart."
Anxious to study the gene in individual cells, Chess and a team that included postdoctoral associate Guilherme Neves, scientist Jacob Zucker and Whitehead Fellow Mark Daly developed a technique for single-cell analysis in fruit flies. The team discovered that different cells in the brain make different types of Dscam protein.
According to Chess, this means each cell contains a distinct Dscam repertoire. "That's what led us to this idea that Dscam might be used to help identify self from nonself," he said.
A similar notion of self vs. nonself has been examined widely in studies of the immune system, where a cell's ability to tell itself apart from foreign cells is crucial to the destruction of virus-infected cells.
"This is a new concept for neurons," Chess said. "It suggests that even while they're driving along, following pathways, they are somehow aware of which parts of the cell membrane surrounding them are their own and which parts belong to different cells."