Abstract
SummaryA 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.
Highlights
The formation of specific synaptic connections between distinct sets of afferent axons and partner neurons during development is pivotal for normal brain function in vertebrates and invertebrates
Fra Is Expressed in R Cells and Target Neurons in the Optic Lobe To gain insights into the role of the Fra guidance receptor in adult visual circuit assembly, we examined its expression in the retina and optic lobe
In the retina (Figures 1C–1F0), colabeling with capricious-Gal4 (Shinza-Kameda et al, 2006) driving membrane-bound green fluorescent protein (GFP) expression revealed that at 24 hr after puparium formation (APF), Fra protein is expressed in R8 cells along their cell bodies, and at 42 and 55 hr in their rhabdomeres, the membrane-rich organelles required for phototransduction in adults
Summary
The formation of specific synaptic connections between distinct sets of afferent axons and partner neurons during development is pivotal for normal brain function in vertebrates and invertebrates. Previous studies implicated the nonclassical Cadherin Flamingo (Fmi) (Hakeda-Suzuki et al, 2011; Senti et al, 2003), the transmembrane protein Golden goal (Gogo) (Hakeda-Suzuki et al, 2011; Mann et al, 2012; Tomasi et al, 2008), and the leucine-rich repeat protein Capricious (Caps) in R8 axon targeting (Shinza-Kameda et al, 2006) While these studies could explain how layer-specific connections of afferent and target neurons are assembled through control of adhesiveness, the mechanisms that precisely position their neurites within one emerging layer remained unclear
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