"They actually produced a Siamese twin embryo," Khokha said. "The piece they cut out from the donor embryo and transplanted into the host embryo was able to redefine the structures in the host embryo to make back structures where the belly would normally form - to induce another head, brain and spinal cord. The tissue they transplanted sent signals to the host to create these new structures."
Since then, scientists have searched for the signaling factors secreted by Spemann's organizer. Dubbed bone morphogenetic protein (BMP) antagonists, these factors block a process that creates belly structures and clear the way for back development.
"It is really in the last 20 years that it has been possible to tease these apart cleanly and develop assays that are good enough to find the molecules involved in the normal process," Harland said.
Postdoctoral fellow Bill Smith and Harland found the first of these BMP antagonists, noggin, in 1992, confirming its activity by repeating Spemann and Mangold's experiment but injecting noggin instead of implanting an organizer from another embryo. They also discovered xnr3, and other researchers isolated three more factors - chordin, follistatin and cerberus. While Harland and his UC Berkeley colleagues found numerous roles for noggin at later stages of development, they were unable to prove that noggin was essential to brain and spinal cord development. Blocking any one of these five factors had only a minimal effect on the fate of the embryo.
Khokha and Harland decided to try blocking more than one, and chose to work in embryos of the frog Xenopus tropicalis,
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Contact: Robert Sanders
rsanders@berkeley.edu
510-643-6998
University of California - Berkeley
9-Mar-2005