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Investigadores de Yale encuentran una molécula que guía a los axones migrantes

Yale Researchers Find Molecule That Guides Migrating Axons

New Haven, Conn. — The human nervous system is like a giant home entertainment system, but instead of 20-odd wires there are trillions of connections that must be made perfectly before the network operates effectively. Scientists have long been fascinated about how the wires in our nervous system, called axons, migrate to form the synaptic connections between neurons that carry out all the functions of the nervous system from thought to movement.
Yale University researchers studying the migration of axons in the spinal cord report Friday in the journal Cell they have found a crucial molecule that helps guide axons on their remarkable journey. A team of scientists led by Elke Stein, Assistant Professor of Molecular, Cellular & Developmental Biology and Cell Biology, showed that a gene linked to the mental retardation phenotype in Downs Syndrome is essential for these axons to make their way across the midline of the spinal cord.

Scientists looking for path-finding axons are particularly interested in the nerve fibers that form at this junction which are known as commissural axons. The midline in the spinal cord is an important region in the nervous system that divides the body into the right and left halves. Recent studies demonstrate specialized cells at the midline play critical roles in regulating the guidance of growing axons in the developing spinal cord by secreting attractive and repulsive signals.

About 20 years ago, netrin-1 was the first such guidance molecules identified. Netrin-1 is a cue that attracts and guides commissural axons over long distances to the midline of the central nervous system. Over the past 15 years, scientists have looked for the receptors expressed at the leading tip of the axons, called the growth cone, which are used to steer these commissural axons to their targets.

Yale researchers report in the Cell paper report that they have found an essential molecule that is expressed on commissural axons called DSCAM, for Down Syndrome Cell Adhesion Molecule. DSCAM has been linked to some of the physical characteristics of Downs's syndrome, which is marked by significant loss of neuronal connections in early development. In collaboration with scientists from Genentech, Stein and her graduate student Alice Ly found that DSCAM, which is expressed on the migrating axons, is necessary for these axons to reach and cross the midline to the source of the attractant, netrin-1. Netrin-1 binds and activates DSCAM and initiates the migration of the axon, much like a key turns the ignition and starts a car.

The researchers showed commissural axons that lack DSCAM do not reach the midline - indicating a loss in axon growth and sense of direction. The Stein laboratory is currently investigating whether DSCAM plays a key role in wiring other parts of the nervous systems as well as its contributions to Down Syndrome.

Other authors of the paper are Geetha Suresh and Yufang Zheng of Yale and Anatoly Nikolaev and Marc Tessier-Lavigne of Genentech Inc.

The study was funded by the March of Dimes, Klingenstein Foundation, McKnight Foundation, the National Science Foundation and the National Institutes of Health.

  PRESS CONTACT: Bill Hathaway 203-432-1322

Credits: Yale University

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