Neurons use fibers from cells called glia and axons from other nerves to migrate to the brain's outer layers. This process relies on many specialized molecules which act as chemical labels to help neurons find the correct pathway. By studying normal neuron migration and factors that can disrupt it, scientists may find ways of preventing or treating epilepsy and many other developmental brain disorders.

      The human brain is a remarkable organ, controlling thoughts, dreams and emotions. But it also is subject to many disorders, such as epilepsy and schizophrenia, which are caused by glitches in brain development only recently recognized.
      For decades, scientists studying embryos have known that brain nerve cells, or neurons, are initially produced in the center of the developing brain. To function normally, neurons must migrate to the brain's cortex, or outer layer, and other structures.
      For the human brain, which contains some 100 billion neurons, migration is a remarkable process that relies on chemical communication between many different cells. In general, the first neurons to migrate form interior brain structures. They are followed by waves of other neurons that travel farther outward. Some neurons, especially those that form outer layers, must travel an incredible distance -- similar to a human walking miles -- at speeds up to 60 millionths of a meter per hour. Once they reach their destination, they send out axons -- long conducting fibers that form connections with other neurons.
      How do neurons know where to migrate? During the early 1970s, researchers examining the developing brains of monkeys discovered that neurons often clung to long fibers of cells called glia. Neurons use these glial fibers, which radiate from the brain's inner to outer surfaces, as a highway to carry them through the brain to their destination. Some neurons also use the axons of other nerves to migrate from one brain area to another.
      Scientists found special molecules on the surface of neurons called adhesion molecules. These substances bind to similar molecules on nearby glial cells or nerve axons. Scientists believe these and other molecules may act as chemical labels telling neurons which paths to follow.

      The discovery of these neuron migration factors is helping researchers:

• Learn how neurons migrate normally.
• Describe the development of neuron migration disorders, including some types of epilepsy and mental retardation.
• Find ways of preventing and treating these disorders.

      Scientists have discovered four major families of adhesion molecules, and they believe hundreds of factors may be at work in developing organisms.
      Many factors -- including radiation, genetic mutations, and drugs such as cocaine and alcohol -- can interfere with the process of neuron migration. For instance, many people who received radiation in the womb during the atomic explosions at Hiroshima and Nagasaki had incomplete neuron migration leading to brain abnormalities. Another good example is childhood epilepsy, in which brain imaging often reveals pockets of misplaced neurons.
      Recently, scientists found several genes which are altered in individual migration disorders and also can lead to disease. In 1991, they located a gene which, when altered, produces Kallmann syndrome, a rare human disorder that results in a missing sense of smell and abnormal genitals. In Kallmann syndrome, the neurons that produce sex hormones and sense odors fail to migrate and cannot function properly. Scientists now believe the Kallmann syndrome gene produces a molecule that marks the pathway to be followed by certain classes of neurons.
      The gene for another neuron migration disorder -- lissencephaly, which causes mental retardation and other problems -- has been isolated, although its precise function is unclear. Some researchers suspect that other diseases, including dyslexia and schizophrenia, are partially due to errors in neuron migration.
      Scientists can locate the genes that control migration factors in mice and determine how they affect development. Eventually, they may be able to replace the missing factors using drugs, gene therapy, or other methods. These and other efforts hold the potential for treating many human brain disorders.

As the brain develops, neurons migrate from the inner surface to form the outer layers. Left: Immature neurons use fibers from cells called glia as highways to carry them to their destinations. Right: A single neuron, shown about 2,500 times its actual size, moves on a glial fiber.

Illustration by Lydia Kibiuk, Copyright © 1995 Lydia Kibiuk.

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