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Axon-Axon Interactions Regulate Topographic Optic Tract Sorting via CYFIP2-Dependent WAVE Complex Function

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Cioni, Jean-Michel 
Wong, Hovy Ho-Wai 
Kodama, Lay 
Harris, William A 


The axons of retinal ganglion cells (RGCs) are topographically sorted before they arrive at the optic tectum. This pre-target sorting, typical of axon tracts throughout the brain, is poorly understood. Here, we show that Cytoplasmic FMR1-Interacting Proteins (CYFIPs) fulfil non-redundant functions in RGCs, with CYFIP1 mediating axon growth and CYFIP2 specifically involved in axon sorting. We find that CYFIP2 mediates homotypic and heterotypic contact-triggered fasciculation and repulsion responses between dorsal and ventral axons. CYFIP2 associates with transporting ribonucleoprotein particles in axons and regulates translation. Axon-axon contact stimulates CYFIP2 to move into growth cones where it joins the actin nucleating WAVE regulatory complex (WRC) in the periphery and regulates actin remodeling and filopodial dynamics. CYFIP2’s function in axon sorting is mediated by its binding to the WRC but not its translational regulation. Together, these findings uncover CYFIP2 as a key regulatory link between axon-axon interactions, filopodial dynamics and optic tract sorting.



CYFIP, WAVE, axon, filopodia, growth cone, optic tract, retinal ganglion cell, topographic sorting, Adaptor Proteins, Signal Transducing, Animals, Animals, Genetically Modified, Axons, Cell Communication, Female, Male, Optic Tract, Retinal Ganglion Cells, Superior Colliculi, Visual Pathways, Xenopus laevis, Zebrafish

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Wellcome Trust (085314/Z/08/Z)
European Research Council (322817)
Wellcome Trust (100329/Z/12/Z)
This work was supported by Wellcome Trust Programme Grants ( 085314 , C.E.H.), Wellcome Trust Investigator Award (SIA 100329/Z/12/Z , W.A.H.), European Research Council Advanced Grant ( 322817 , C.E.H.), EMBO Long Term Fellowship ( ALTF849-2013 , J.-M.C.), Cambridge Trust, Croucher Foundation, and Sir Edward Youde Memorial Fund (H.H.W.).