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At the Switch of a Gene
At the Switch of a Gene

Before birth, before a fly or bird or human is even in the form of an egg, life often teeters for a moment on a single gene.

For the fruit fly, common in scientists' labs across the world as a model to understand the choreography of genes, proteins and their interactions, one of those decisive moments arrives when the cells that surround a forming egg suddenly stop dividing as if a switch were flipped. These "follicular" cells, in an envelope enclosing a ball of other cells that comprise the egg-to-be, continue to replicate their DNA, but at a specific point, they stop spending their energy splitting into more individual cells, and they start investing more in providing nutrients to the proto-egg that they encase. The mystery here is how cells transition from one phase to the next.

Wu-Min Deng, assistant professor of biological science, had already discovered that a cascade of interactions named after a gene and its resulting protein nicknamed "Notch" plays a major role in shutting down these supporting cells' proliferation. Building on that finding, this March the journal Developmental Cell carried news of Deng's latest findings.

Deng and graduate student Jianjun Sun found that when follicular cells are sluggish to produce a protein nicknamed "Hindsight," they continue to divide when they are supposed to stop. And chances are, this unchecked proliferation will essentially kill the forming egg.

As it turns out, Deng's research also revealed that Hindsight links the Notch pathway in a kind of bridge to another protein nicknamed "Hedgehog," which normally encourages follicular cells to continue dividing. Essentially, Hindsight tells Hedgehog to stop so the cells can switch into a new gear.

Both Notch and Hedgehog pathways are major players in development that have been linked to human diseases, including some types of cancer.

"Cells have to proliferate," Deng said. "But they have to be controlled."

In cancer, there is a broken genetic switch that allows cells to keep dividing with no control. Deng's research suggests a possible way to fix that switch. —C.S.