Localized netrins act as positional cues to control layer-specific targeting of photoreceptor axons in Drosophila

Neuron. 2012 Jul 12;75(1):80-93. doi: 10.1016/j.neuron.2012.04.037.


A shared feature of many neural circuits is their organization into synaptic layers. However, the mechanisms that direct neurites to distinct layers remain poorly understood. We identified a central role for Netrins and their receptor Frazzled in mediating layer-specific axon targeting in the Drosophila visual system. Frazzled is expressed and cell autonomously required in R8 photoreceptors for directing their axons to the medulla-neuropil layer M3. Netrin-B is specifically localized in this layer owing to axonal release by lamina neurons L3 and capture by target neuron-associated Frazzled. Ligand expression in L3 is sufficient to rescue R8 axon-targeting defects of Netrin mutants. R8 axons target normally despite replacement of diffusible Netrin-B by membrane-tethered ligands. Finally, Netrin localization is instructive because expression in ectopic layers can retarget R8 axons. We propose that provision of localized chemoattractants by intermediate target neurons represents a highly precise strategy to direct axons to a positionally defined layer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Axons / chemistry
  • Axons / metabolism*
  • Cues*
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster
  • Nerve Growth Factors / biosynthesis
  • Nerve Growth Factors / metabolism*
  • Netrin Receptors
  • Netrins
  • Photoreceptor Cells, Invertebrate / chemistry
  • Photoreceptor Cells, Invertebrate / metabolism*
  • Receptors, Cell Surface / biosynthesis*
  • Visual Pathways / chemistry
  • Visual Pathways / metabolism


  • Drosophila Proteins
  • Nerve Growth Factors
  • Netrin Receptors
  • Netrins
  • Receptors, Cell Surface
  • fra protein, Drosophila
  • netrin-2