At the time when Spemann won the Nobel Prize, the Organizer was all the rage. Scientists sought the mysterious chemical that could induce the entire body plan. But just as popular culture has yo-yos and Tickle Me Elmo dolls, so science has fads that wax and wane. By the 1970s, the Organizer was viewed as little more than a curiosity, a clever anecdote in the history of embryology. The reason for this fall from grace was that no one could decipher the mechanisms that made it work.
The discovery of Hox genes in the 1980s changed everything. In the early 1990s, when the Organizer concept was still decidedly unfashionable, Eddie De Robertis's laboratory at UCLA was looking for Hox genes in frogs, using techniques like Levine and McGinnis's. The search was broad and it netted many different kinds of genes. One of these had a very special pattern of activity. It was active at the exact site in the embryo that contains the Organizer, and it was active at exactly the right time of development. I can only imagine what De Robertis felt when he found that gene. He was looking at the Organizer, and there in the Organizer was a gene that seemed specifically to control it or be linked to its activity in the embryo. The Organizer was back.
Organizer genes started popping up in laboratories everywhere. While doing a different kind of experiment, Richard Harland at Berkeley found another gene, which he called Noggin. Noggin does exactly what an Organizer gene should. When Harland took some Noggin and injected it into the right place in an embryo, it functioned exactly like the Organizer. The embryo developed two body axes, including two heads.
Are De Robertis's gene and Noggin the actual bits of DNA that make up the Organizer? The answer is yes and no. Many genes, including these two, interact to organize the body plan. Such systems are complex, because genes can play many different roles during development. Noggin, for example, plays a role in the development of the body axis but is also involved with a host of other organs. Furthermore, genes do not act alone to specify complicated cell behaviors like those we see in head development. Genes interact with other genes at all stages of development. One gene may inhibit the activity of another or promote it. Sometimes many genes interact to turn another gene on or off. Fortunately, new tools allow us to study the activity of thousands of genes in a cell at once. Couple this technology with new computer-based ways of interpreting gene function and we have enormous potential to understand how genes build cells, tissues, and bodies.
Understanding these complex interactions between batteries of genes sheds light on the actual mechanisms that build bodies. Noggin serves as a great example. Noggin alone does not instruct any cell in the embryo about its position on the top-bottom axis; rather, it acts in concert with several other genes to do this. Another gene, BMP-4, is a bottom gene; it is turned on in cells that will make the bottom, or belly side, of an embryo. There is an important interaction between BMP-4 and Noggin. Wherever Noggin is active, BMP-4 cannot do its job. The upshot is that Noggin does not tell cells to develop as "cells on the top of the body" instead, it turns off the signal that would make them bottom cells. These off-on interactions underlie virtually all developmental processes.
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