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

Jean-Michel Cioni1, Hovy Ho-Wai Wong1, Dario Bressan2

  • 1Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3DY, UK.

Neuron
|March 9, 2018
PubMed
Summary
This summary is machine-generated.

Cytoplasmic FMR1-interacting protein 2 (CYFIP2) is crucial for sorting retinal ganglion cell axons. CYFIP2 regulates axon-axon interactions and actin dynamics, guiding optic tract sorting.

Keywords:
CYFIPWAVEaxonfilopodiagrowth coneoptic tractretinal ganglion celltopographic sorting

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Cell Biology

Background:

  • Axon guidance and sorting are fundamental processes for establishing neural circuits.
  • The mechanisms underlying topographic sorting of axons before reaching their targets remain largely unknown.
  • Cytoplasmic FMR1-interacting proteins (CYFIPs) are implicated in neuronal development, but their specific roles in axon sorting are unclear.

Purpose of the Study:

  • To investigate the functions of CYFIP1 and CYFIP2 in retinal ganglion cell (RGC) axon development and sorting.
  • To elucidate the molecular mechanisms by which CYFIP2 mediates axon sorting in the optic tract.

Main Methods:

  • Utilized genetic manipulation in RGCs to assess CYFIP1 and CYFIP2 functions.
  • Analyzed axon morphology and sorting patterns in vivo.
  • Investigated protein interactions and localization using biochemical and imaging techniques.
  • Examined the role of CYFIP2 in regulating actin dynamics and translation in axons.

Main Results:

  • CYFIP1 and CYFIP2 exhibit non-redundant functions in RGCs; CYFIP1 promotes axon growth, while CYFIP2 is essential for axon sorting.
  • CYFIP2 mediates contact-dependent fasciculation and repulsion between dorsal and ventral axons.
  • CYFIP2 associates with axonal ribonucleoprotein particles and influences translation.
  • Axon-axon contact triggers CYFIP2 translocation to growth cones, where it interacts with the WAVE regulatory complex (WRC) to modulate actin remodeling and filopodial dynamics.

Conclusions:

  • CYFIP2 plays a critical role in the topographic sorting of RGC axons.
  • CYFIP2 acts as a molecular link between axon-axon interactions, growth cone actin dynamics, and the precise sorting required for optic tract formation.
  • The function of CYFIP2 in axon sorting relies on its interaction with the WRC, rather than its translational regulatory activity.