A Network of Cadherin-Mediated Interactions Polarizes Growth Cones to Determine Targeting Specificity

• Published in: Cell Vol. 154; no. 2; pp. 351 - 364
• Main Authors: Schwabe, Tina, Neuert, Helen, Clandinin, Thomas R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18.07.2013
• Subjects: Animals; Axons - metabolism; cadherins; Cadherins - metabolism; direct contact; Drosophila; Drosophila melanogaster - growth & development; Drosophila melanogaster - metabolism; Drosophila Proteins - metabolism; Growth Cones - metabolism; Photoreceptor Cells, Invertebrate - metabolism; photoreceptors; pseudopodia; Retina - metabolism; Synapses
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2013.06.011

Neuronal growth cones select synaptic partners through interactions with multiple cell surfaces in their environment. Many of these interactions are adhesive, yet it is unclear how growth cones integrate adhesive cues to direct their movements. Here, we examine the mechanisms that enable photoreceptors in the Drosophila visual system to choose synaptic partners. We demonstrate that the classical cadherin, N-cadherin, and an atypical cadherin, Flamingo, act redundantly to instruct the targeting choices made by every photoreceptor axon. These molecules gradually bias the spatial distribution of growth cone filopodia, polarizing each growth cone toward its future synaptic target before direct contact with the target occurs. We demonstrate that these molecules are localized to distinct subcellular domains and create a network of adhesive interactions distributed across many growth cones. Because this network comprises multiple redundant interactions, a complex wiring diagram can be constructed with extraordinary fidelity, suggesting a general principle. [Display omitted] •Cadherins determine targeting specificity by polarizing growth cones•Cadherins are targeted to specific growth cone subdomains•Cellular and molecular redundancies achieve targeting with high fidelity•A complex interaction network polarizes growth cones toward their targets The relative—not absolute—levels of two cadherins (N-cadherin and Flamingo) modulate adhesion among photoreceptor growth cones in Drosophila, creating a network of interactions that directs photoreceptor axons to specific synaptic targets in the brain.