SUMMARY | FULL STORY
GENETICS
Level-headed Stardust Knows Which Way Is Up
Polarity Gene Yields Clues to Organization of Cell Signaling, Structural Growth
In 1980, in what might be called the early morning hours of modern genetics, two Heidelberg researchers made a stunning announcement. By making random dings in fruit fly DNA, thereby creating discrete mutations, they had identified 150 genes that control the tiny insect's early embryonic development.
The surface of an epithelial cell resembles the multitiered facade of a building with polarity proteins arranged in bands, one above the other. The stardust protein associates with crumbs as shown above.
Four of the genes would later be found to control the intrinsic north-south orientation, or polarity, of embryonic epithelial cells. Mutant versions of the genes produce striking disruptions in the embryo.
"It looked like you took a bazooka and just blew it into an embryo--that's what you would get," said Norbert Perrimon, HMS professor of genetics. Other researchers would go on to characterize and clone three of the genes, aptly named bazooka, shotgun, and crumbs. The fourth, stardust, remained an abstraction--until now.
"The cloning of stardust is an important discovery because there are only a few polarity genes known," says Norbert Perrimon, shown here with Beth Stronach. Photo by Pam Murray
Working with Perrimon, Beth Stronach, HMS research fellow in genetics, has cloned the
stardust gene. With colleagues at the University of California, San Francisco, the researchers are beginning to understand how the gene works to set up the basic top-down architecture of the epithelial cells that line the gut, skin, and many other organs of the embryo. Their discoveries, reported in the Dec. 6
Nature, could help researchers answer some of the fundamental questions of biology: how do cells send and receive signals? How do tissues and organs take shape? They could also hold clues to ongoing mysteries such as how cancers arise.
The addition of stardust to the known constellation of polarity genes opens the door to new research problems. "Our aim now is to understand what those polarity proteins are really doing," Perrimon said. "Why do you need to subdivide the surface of the cell? They are like landmarks, but what is their real function?"
The search for answers could lead to a journey as unpredictable as the one that brought Perrimon to ask such questions. "We started with signal transduction," he said. "That led us to polarity. Now most of the lab works on morphogenesis. Let's just say, we are evolving."
--Misia Landau
Copyright 2001 by the President and Fellows of Harvard College
