(5 of 10)
What guides an axon on its incredible voyage is a "growth cone," a creepy, crawly sprout that looks something like an amoeba. Scientists have known about growth cones since the turn of the century. What they didn't know until recently was that growth cones come equipped with the molecular equivalent of sonar and radar. Just as instruments in a submarine or airplane scan the environment for signals, so molecules arrayed on the surface of growth cones search their surroundings for the presence of certain proteins. Some of these proteins, it turns out, are attractants that pull the growth cones toward them, while others are repellents that push them away.
THE FIRST STIRRINGS
Up to this point, genes have controlled the unfolding of the brain. As soon as axons make their first connections, however, the nerves begin to fire, and what they do starts to matter more and more. In essence, say scientists, the developing nervous system has strung the equivalent of telephone trunk lines between the right neighborhoods in the right cities. Now it has to sort out which wires belong to which house, a problem that cannot be solved by genes alone for reasons that boil down to simple arithmetic. Eventually, Berkeley's Goodman estimates, a human brain must forge quadrillions of connections. But there are only 100,000 genes in human DNA. Even though half these genes--some 50,000--appear to be dedicated to constructing and maintaining the nervous system, he observes, that's not enough to specify more than a tiny fraction of the connections required by a fully functioning brain.
In adult mammals, for example, the axons that connect the brain's visual system arrange themselves in striking layers and columns that reflect the division between the left eye and the right. But these axons start out as scrambled as a bowl of spaghetti, according to Michael Stryker, chairman of the physiology department at the University of California at San Francisco. What sorts out the mess, scientists have established, is neural activity. In a series of experiments viewed as classics by scientists in the field, Berkeley's Shatz chemically blocked neural activity in embryonic cats. The result? The axons that connect neurons in the retina of the eye to the brain never formed the left eye-right eye geometry needed to support vision.
But no recent finding has intrigued researchers more than the results reported in October by Corey Goodman and his Berkeley colleagues. In studying a deceptively simple problem--how axons from motor neurons in the fly's central nerve cord establish connections with muscle cells in its limbs--the Berkeley researchers made an unexpected discovery. They knew there was a gene that keeps bundles of axons together as they race toward their muscle-cell targets. What they discovered was that the electrical activity produced by neurons inhibited this gene, dramatically increasing the number of connections the axons made. Even more intriguing, the signals amplified the activity of a second gene--a gene called CREB.