Protein determines fruit fly physique.

Protein determines fruit fly physique

Nearly 100 years ago, scientists first published speculation that "a sort of stuff" in young embryos might direct the mysterious process of cell differentiation, development and limb pattern formation as an animal grows from a fertilized egg to adulthood. Now, using a combination of genetic, developmental and molecular biologic techniques, West German researchers have provided the first clear evidence that such a stuff exists in extremely young fruit fly embryos and that it organizes the process of differentiation along the fly's longitudinal axis. The research, published in the July 1 CELL, is the latest in a series of groundbreaking papers by Christian Nusslein-Volhard and her associates at the Max-Planck-Institut fur Entwicklungsbiologie in Tubingen.

"The work has been done absolutely beatifully," says Matthew Scott, a developmental biologist who works with the fruit fly, Drosohila, at the Universty of Colorado in Boulder. "It's one of our nicest studies that's been done in developmental genetics in a long time."

According to the morphogenetic model of development, first proposed in 1897, a biologically active chemical is secreted from one end of an embryo and spreads to other parts in decreasing amounts. The theory says cells can "calculate" where they are in this chemical gradient -- and differentiate accordingly -- by sensing the local concentration of the chemical.

To date, perhaps the most convincing candidate morphogen is retinoic aci, which plays major role in limb pattern formation in chick embryos (SN: 6/27/87, p.406). Looking at an even earlier stage of development in Drosophila embryos, Nusslein-Volhard and Wolfgand Driever used labeled antibodies to show that a protein called bicoid diffuses in a stee, head-to-tail gradient within hours after the first cell begins to divide. And by looking at genetic variants of flies that produce different amounts of bicoid, they show that the protein determines the cell differentiation process in a concentration-dependent manner. Specifically, the higher the concentration of bicoid near the head of the embryo, the further various body parts are pushed back toward the tail.

The research shows that cells must have some mechanism for reading the absolute concentration of bicoid, says Welcome Bender, a specialist in Drosophila development at Harvard Medical School in Boston. Scientists have yet to discover what that mechanism is, but the protein appears to have a so-called homeobox sequence, which suggests it may act directly on DNA to regulate gene expression.