Frazzled promotes growth cone attachment at the source of a Netrin gradient in the Drosophila visual system

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Abstract

Axon guidance is proposed to act through a combination of long- and short-range attractive and repulsive cues. The ligand-receptor pair, Netrin (Net) and Frazzled (Fra) (DCC, Deleted in Colorectal Cancer, in vertebrates), is recognized as the prototypical effector of chemoattraction, with roles in both long- and short-range guidance. In the Drosophila visual system, R8 photoreceptor growth cones were shown to require Net-Fra to reach their target, the peak of a Net gradient. Using live imaging, we show, however, that R8 growth cones reach and recognize their target without Net, Fra, or Trim9, a conserved binding partner of Fra, but do not remain attached to it. Thus, despite the graded ligand distribution along the guidance path, Net-Fra is not used for chemoattraction. Based on findings in other systems, we propose that adhesion to substrate-bound Net underlies both long- and short-range Net-Fra-dependent guidance in vivo, thereby eroding the distinction between them.

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Orkun Akin

Department of Biological Chemistry, Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, United States

For correspondence
akin.orkun@gmail.com

Competing interests
The authors declare that no competing interests exist.
S Lawrence Zipursky

Department of Biological Chemistry, Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, United States

For correspondence
lzipursky@mednet.ucla.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-5630-7181

Funding

Howard Hughes Medical Institute

S Lawrence Zipursky

Damon Runyon Cancer Research Foundation

Orkun Akin

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.