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Netrins guide Drosophila commissural axons at short range

Nature Neuroscience volume 9, pages 188–194 (2006)Cite this article

Abstract

Netrins are secreted axon guidance molecules required for commissure formation in a wide range of animal species, including Caenorhabditis elegans, Drosophila melanogaster and mice. They are generally thought to function as chemoattractants, acting at a distance to direct commissural axon growth toward the midline of the central nervous system. We show here, however, that D. melanogaster commissural axons still orient normally and reach the midline even in the complete absence of netrins, though some of them fail to cross the midline. Tethering endogenous netrin to the membrane selectively disrupts its long-range but not short-range activity, yet still allows normal commissure formation. We therefore propose that netrins act in commissural axon guidance as short-range cues that promote midline crossing, not as long-range chemoattractants.

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Figure 1: Either netrin is sufficient for commissure formation.
Figure 2: Axons orient and extend normally toward the midline in NetABΔ double mutants, but some fail to cross.
Figure 3: Tethering NetB to the membrane.
Figure 4: Membrane-tethered netrin functions in commissure formation.
Figure 5: Short- and long-range repulsion by NetA and NetB.
Figure 6: Tethering NetB to the membrane blocks long- but not short-range repulsion.

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Acknowledgements

We thank C. Rickert and G. Technau for their skill, patience and hospitality in teaching M.B. how to perform DiI labeling; A. Graf and K. Paiha for technical assistance; and F. Schnorrer and G. Gilestro for comments on the manuscript. We also thank the Drosophila Genetic Resource Center in Kyoto and the Gene Disruption Project for P-element stocks. This work was supported by a grant from the Austrian Science Fund.

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  1. Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr-Gasse 3-5, Vienna, A-1030, Austria

    Marko Brankatschk & Barry J Dickson

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Correspondence to Barry J Dickson.

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Supplementary information

Supplementary Fig. 1

Targeting NetB. (PDF 67 kb)

Supplementary Video 1

ato axons in wild-type embryos. Time-lapse of an ato-GAL4 UAS-mCD8-GFP embryo, showing ato sensory axons entering and arborizing within the CNS. The embryo was scanned at 90-second intervals, from stage 14 until stage 16 (total time 2:22:30). (MOV 2325 kb)

Supplementary Video 2

ato axons expressing Unc5 in NetAΔNetBmyc. embryos. Time-lapse of a NetAΔ NetBmyc. ato-GAL4 UAS-Unc5 UAS-mCD8-GFP embryo, showing ato sensory axons extending toward but not entering the CNS. The embryo was scanned at 90-second intervals, from stage 14 until stage 16 (total time 2:22:30). (MOV 2394 kb)

Supplementary Video 3

ato axons expressing Unc5 in NetAΔNetB™. embryos. Time-lapse of a NetAΔ NetB™. ato-GAL4 UAS-Unc5 UAS-mCD8-GFP embryo, showing ato sensory axons entering and arborizing within the CNS. The embryo was scanned at 90-second intervals, from stage 14 until stage 16 (total time 2:22:30). (MOV 2322 kb)

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Brankatschk, M., Dickson, B. Netrins guide Drosophila commissural axons at short range. Nat Neurosci 9, 188–194 (2006). https://doi.org/10.1038/nn1625

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