( ive of the more common laboratory frog ...)Scientists discover that three overlapping signals in embryo help get the backbone right

ive of the more common laboratory frog Xenopus laevis. X. tropicalis is easier to work with, because it, like humans, is diploid, that is, it has only two copies of each gene, instead of four, as in the tetraploid X. laevis. Lab specimens of X. tropicalis also have less genetic variation than outbred populations of X. laevis, and the genome of X. tropicalis has been sequenced. Harland is pioneering the use of X. tropicalis in genetic studies, creating numerous mutants that can be used to explore the role of various genes in development.

Using standard knock-out techniques, their team inactivated the function of these BMP antagonists in various combinations, finding the most dramatic effect by simultaneously knocking out noggin, follistatin, and chordin.

Harland noted that the signaling pathway they blocked is one of several developmental pathways proceeding at the same time in the embryo. While BMP antagonists allow the formation of the back and belly, another group of antagonists creates the head and tail, while a third sets up left and right.

"It's been interesting that what one thinks of embryologically as the dominant signaling center actually is a source of a cocktail of inhibitors," he said, "so inhibition is just as specific a signal in the embryo as is an activating signal."

Since they discovered noggin, Harland and his colleagues have shown that in later stages of development, this protein factor is critical in laying down cartilage to make joints, and even plays an important role after birth. Recently, he and Stanford University colleagues showed that noggin may be important in preventing the premature fusion of the bones in the skull, and thus may be critical to allowing the brain to grow larger after birth. All of these findings are from mice or amphibians, but the researchers say that the same is almost certain to be the case in humans.

"One of the things that's been nicely shown is that the organizer itself, whil
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Source:University of California - Berkeley

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