Localized netrins act as positional cues to control layer-specific targeting of photoreceptor axons in Drosophila.
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.
Division of Molecular Neurobiology, MRC National Institute for Medical Research, London, UK.
Katarina
K
Timofeev
Willy
W
Joly
Dafni
D
Hadjieconomou
Iris
I
Salecker
D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000737:chemistry / Q000378:metabolism*; D003463:Cues; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism*; D004331:Drosophila melanogaster; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000378:metabolism*; D000075386:Netrin Receptors; D000075385:Netrins; D017956:Photoreceptor Cells, Invertebrate / Q000737:chemistry / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000096:biosynthesis*; D014795:Visual Pathways / Q000737:chemistry / Q000378:metabolism
D029721:Drosophila Proteins; D009414:Nerve Growth Factors; D000075386:Netrin Receptors; D000075385:Netrins; D011956:Receptors, Cell Surface; C000617310:fra protein, Drosophila; C088894:netrin-2