Errant nerve cells risk a clockwork death

October 21, 1999--Fetal nerve cells growing along the spinal cord literally race against the clock to create connections within the developing nervous system. Newly published studies by investigators at the Howard Hughes Medical Institute (HHMI) at the University of California, San Francisco (UCSF), show that growing neurons must reach a specific intermediate destination by a certain time or risk not receiving life-sustaining chemical signals from specialized spinal cord tissue.

According to Marc Tessier-Lavigne, an HHMI investigator at UCSF, the discovery likely reveals a new fail-safe mechanism that ensures proper wiring of the nervous system. This checkpoint allows the burgeoning nervous system to winnow wayward neurons whose meanderings could cause dangerous miswiring of neural circuitry.

Tessier-Lavigne and former postdoctoral fellow Hao Wang, who is now a scientist at the Merck Research Laboratories, reported their discovery in the October 21, 1999, issue of Nature.

The new mechanism for intermediate control of neural wiring is different from, albeit complementary to, the well-known "final target-derived neurotrophic system," which governs the survival of neurons once they reach their final destination in the nervous system and kills off neurons that inadvertently reach the wrong target. The newly described "intermediate control" system functions solely to ensure accuracy in neural connections.

"In the traditional, final target-derived neurotrophic system," Tessier-Lavigne explained, "the long cable-like axons of nerve cells must compete for limited life-giving chemical signals known as neurotrophins when they reach their final target." Competition for limited amounts of neurotrophins at a target cell kills off excess nerve cells, leaving only the proper population of neurons necessary for wiring a given neural circuit.

"We speculate that

Contact: Jim Keeley
Howard Hughes Medical Institute

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