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But what awes scientists who study the brain, what still stuns them, is not that things occasionally go wrong in the developing brain but that so much of the time they go right. This is all the more remarkable, says Berkeley's Shatz, as the central nervous system of an embryo is not a miniature of the adult system but more like a tadpole that gives rise to a frog. Among other things, the cells produced in the neural tube must migrate to distant locations and accurately lay down the connections that link one part of the brain to another. In addition, the embryonic brain must construct a variety of temporary structures, including the neural tube, that will, like a tadpole's tail, eventually disappear.
What biochemical magic underlies this incredible metamorphosis? The instructions programmed into the genes, of course. Scientists have recently discovered, for instance, that a gene nicknamed "sonic hedgehog" (after the popular video game Sonic the Hedgehog) determines the fate of neurons in the spinal cord and the brain. Like a strong scent carried by the wind, the protein encoded by the hedgehog gene (so called because in its absence, fruit-fly embryos sprout a coat of prickles) diffuses outward from the cells that produce it, becoming fainter and fainter. Columbia University neurobiologist Thomas Jessell has found that it takes middling concentrations of this potent morphing factor to produce a motor neuron and lower concentrations to make an interneuron (a cell that relays signals to other neurons, instead of to muscle fibers, as motor neurons do).
Scientists are also beginning to identify some of the genes that guide neurons in their long migrations. Consider the problem faced by neurons destined to become part of the cerebral cortex. Because they arise relatively late in the development of the mammalian brain, billions of these cells must push and shove their way through dense colonies established by earlier migrants. "It's as if the entire population of the East Coast decided to move en masse to the West Coast," marvels Yale University neuroscientist Dr. Pasko Rakic, and marched through Cleveland, Chicago and Denver to get there.
But of all the problems the growing nervous system must solve, the most daunting is posed by the wiring itself. After birth, when the number of connections explodes, each of the brain's billions of neurons will forge links to thousands of others. First they must spin out a web of wirelike fibers known as axons (which transmit signals) and dendrites (which receive them). The objective is to form a synapse, the gap-like structure over which the axon of one neuron beams a signal to the dendrites of another. Before this can happen, axons and dendrites must almost touch. And while the short, bushy dendrites don't have to travel very far, axons--the heavy-duty cables of the nervous system--must traverse distances that are the microscopic equivalent of miles.