Embryonic growth: cues and miscues.

Embryonic growth: Cues and miscues

If this were a monster movie, the opening scene would surely grab the audience. In a quiet laboratory, scientists snip a piece of tissue from a blob of cells destined to develop into a tadpole. Normally, the tissue could only form skin cells, but the scientists have other designs for this embryonic fragment. After soaking in a solution of nutrients and mouse cells, the cultured tissue elongates -- the first sign that something out of the ordinary has happened. The next day, an amphibian mouth takes shape at one end, and the other end begins twitching. The outline of a brain appears 24 hours later. And finally, the piece de resistance: Within the mass emerges the unmistakable black eyeball of a tadpole peering out of the petri dish.

The scenario is science, not fiction.

In the Aug. 3 SCIENCE, three researchers report that they have isolated a mouse protein that alters the fate of cultured epidermal tissue from frog embryos. Instead of making skin, the tissue forms an "embryoid" -- a miniature embryo including muscle, nerves and even eyes.

"It's quite an amazing transformation to start with just skin cells and then make [organized parts of] an embryo," says Douglas A. Melton of Harvard University, who did the work with graduate student Sergei Sokol and Gordon G. Wong of the Genetics Institute in Cambridge, Mass.

Since 1987, several research groups have identified peptide growth factors, all derived from adult frogs, that trigger development of nerve cells when added to cultured frog embryonic tissue, Melton notes -- but none of the compounds induced eye and brain formation. Moreover, he says, the new work marks the first time researchers have isolated from another animal a growth factor that induces changes in frog embryos.

The results suggest that the mouse-derived protein, known as PIF, may occur naturally and play a similar role in several animal species, Melton asserts. He cautions, however, that researchers have not yet tested PIF's ability to alter embryonic tissue from mice.

While scientists have speculated that an assortment of growth factors may occur naturally in embryos to direct cell development, none of these compounds had been detected in untreated, normally developing tissue. But Melton told SCIENCE NEWS that he and other co-workers recently cloned a gene from intact frog embryos and found that this gene induces cells predisposed to forming skin tissue to make nerve tissue and muscles instead.

The protein encoded by this naturally occurring gene, he says, "is virtually identical to" the mouse-derived PIF, clinching the protein's role in guiding embryonic development.

Melton thinks PIF influences one of the earliest and most crucial stages in amphibian embryo development. Newly fertilized frog eggs hold only two kinds of cells -- endodermal and ectodermal. Endodermal cells form the gut, while ectodermal cells, if left to their own devices, form skin. But when ectodermal cells receive chemical cues from adjacent endodermal cells, they transform into cells that make nerve and muscle tissue.

PIF appears to resemble the critical chemical signal produced by endodermal cells, Melton says. Alternatively, PIF may act indirectly, triggering endodermal cells to secrete other essential chemical cues. "Without PIF, there would be no further development -- only skin and guts, without bone, muscles or nerves," he notes. Melton suggests that several growth factors may work at different stages to ensure proper embryo development.

The team is now examining PIF's similarity to a recently characterized protein that also transforms cultured ectodermal cells into nerve- and muscle-makers. Jack C. Smith and his co-workers at Innogenetics in Ghent, Belgium, and the National Institute for Medical Research in London, England, report in the June 21 NATURE that this compound, known as XTC-MIF, appears structurally similar to activin, a human growth factor. Innogenetics researchers who collaborated with Dutch scientists describe identical results in the same issue.