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Neurobiology

Frazzled precision guides axons

Nature volume 406, pages 841–843 (2000)Cite this article

A functional nervous system depends on an intricate, finely tuned network of neuronal connections. During development, axons and dendrites, the specialized projections of a neuron, extend from the neuronal cell body over what are often long distances to establish contact with their targets. To ensure accurate targeting, axons and dendrites use attractive and repulsive guidance cues along their trajectories. Using the fruitfly Drosophila melanogaster as a model system, Hiramoto and colleagues, writing on page 886 of this issue1, offer mechanistic insight into how secreted, diffusible cues can provide precise guidance information. The authors show that a member of the Netrin family of diffusible guidance proteins is captured far from its site of synthesis and presented to approaching axons by its binding partner, a protein called Frazzled. The Netrin protein thereby instructs growing axons to follow a precise trajectory within the central nervous system (CNS).

Netrins are potent secreted guidance cues3,4. In organisms from worms to mammals, Netrins attract axons from specific neuronal populations that cross from one side of the body to the other, towards the midline of the CNS. Long-range attraction by Netrin is mediated by receptors of the Deleted in Colorectal Cancer (DCC) protein family, which includes the Drosophila protein Frazzled. Intriguingly, Netrins can repel other populations of neurons that are directed away from the midline. Long-range repulsion by Netrin is mediated by a receptor complex that includes DCC and a member of the UNC-5 family of cell-surface-located receptors5,6. Netrin receptors can be found on the surface of the growing axon and, on binding secreted Netrins, they send signals inside the axon to tell it which way to go. But in Drosophila , Frazzled is sometimes required not on the growing axons, but rather in their intermediate targets. How might Frazzled be used here?

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Figure 1: Guiding axon trajectories in developing embryos.

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Authors and Affiliations

  1. the Department of Neuroscience, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, 21205, Maryland, USA

    Roman J. Giger & Alex L. Kolodkin

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  1. Roman J. Giger
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  2. Alex L. Kolodkin
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Correspondence to Alex L. Kolodkin.

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Giger, R., Kolodkin, A. Frazzled precision guides axons. Nature 406, 841–843 (2000). https://doi.org/10.1038/35022694

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