New Class Of Molecular Cues Guides Nervous System Wiring

March 19, 1999—In the developing nervous system, a group of molecular road signs directs growing nerve cells toward their correct destination. Now, collaborating groups of Howard Hughes Medical Institute (HHMI) investigators have discovered a new type of road sign that, depending upon the conditions, either repels growing neurons or triggers neurons to sprout new connections.

As reported in three articles in the March 19, 1999, issue of the journal Cell, this seemingly contradictory "Stop-and-Go" behavior of the protein, Slit, opens an intriguing new chapter in understanding how the nervous system is wired, say the scientists. If the researchers can understand the machinery controlling such wiring decisions, their insights may lead to new approaches to regrow or repair damaged or severed spinal cord nerves.

The Cell articles describe how the two HHMI laboratories, headed by long-time friends and scientific collaborators Corey Goodman and Marc Tessier-Lavigne, worked together closely to study the Slit protein in two very different organisms—fruit flies and mammals.

In a first set of studies, Goodman, an HHMI investigator at the University of California at Berkeley, and HHMI associate Tom Kidd and colleague Kim Bland used genetic mutant screening studies of the fruit fly Drosophila to pinpoint the Slit protein as a key repellent molecule in developing fly embryos. The group had previously shown that the roundabout, or Robo, protein is a repulsive receptor on the surface of growing axons. They also demonstrated that Robo controlled whether axons crossed or recrossed the center, or "midline," of the fruit fly nervous system—to properly connect the brain’s two halves— by responding to an unknown midline repellent signal.

In the current study, Goodman and hi

Contact: Jim Keeley
Howard Hughes Medical Institute

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