ZFIN ID: ZDB-PUB-190716-14
Axon-Axon Interactions Regulate Topographic Optic Tract Sorting via CYFIP2-Dependent WAVE Complex Function
Cioni, J.M., Wong, H.H., Bressan, D., Kodama, L., Harris, W.A., Holt, C.E.
Date: 2018
Source: Neuron   97: 1078-1093.e6 (Journal)
Registered Authors: Harris, William A.
Keywords: CYFIP, WAVE, axon, filopodia, growth cone, optic tract, retinal ganglion cell, topographic sorting
MeSH Terms:
  • Adaptor Proteins, Signal Transducing/analysis
  • Adaptor Proteins, Signal Transducing/metabolism*
  • Animals
  • Animals, Genetically Modified
  • Axons/chemistry
  • Axons/metabolism*
  • Cell Communication/physiology*
  • Female
  • Male
  • Optic Tract/chemistry
  • Optic Tract/cytology
  • Optic Tract/metabolism*
  • Retinal Ganglion Cells/chemistry
  • Retinal Ganglion Cells/metabolism
  • Superior Colliculi/chemistry
  • Superior Colliculi/metabolism
  • Visual Pathways/chemistry
  • Visual Pathways/cytology
  • Visual Pathways/metabolism*
  • Xenopus laevis
  • Zebrafish
PubMed: 29518358 Full text @ Neuron
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) fulfill 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.