ADF/Cofilin-Mediated Actin Retrograde Flow Directs Neurite Formation in the 
Developing Brain

Flynn, Kevin C.; Hellal, Farida; Neukirchen, Dorothee; Jacob, Sonja; Tahirovic, Sabina; Dupraz, Sebastian; Stem, Sina; Garvalov, Boyan K.; Gurniak, Christine; Shaw, Alisa E.; Meyn, Liane; Wedlich-Soeldner, Roland; Bamburg, James R.; Small, J. Victor; Witke, Walter; Bradke, Frank

doi:10.1016/j.neuron.2012.09.038

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ADF/Cofilin-Mediated Actin Retrograde Flow Directs Neurite Formation in the Developing Brain

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Hellal, Farida
Max Planck Research Group: Axonal Growth and Regeneration / Bradke, MPI of Neurobiology, Max Planck Society;

/persons/resource/persons39008

Neukirchen, Dorothee
Max Planck Research Group: Axonal Growth and Regeneration / Bradke, MPI of Neurobiology, Max Planck Society;

/persons/resource/persons39093

Tahirovic, Sabina
Max Planck Research Group: Axonal Growth and Regeneration / Bradke, MPI of Neurobiology, Max Planck Society;

/persons/resource/persons38846

Garvalov, Boyan K.
Max Planck Research Group: Axonal Growth and Regeneration / Bradke, MPI of Neurobiology, Max Planck Society;

/persons/resource/persons38995

Meyn, Liane
Max Planck Research Group: Axonal Growth and Regeneration / Bradke, MPI of Neurobiology, Max Planck Society;

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Wedlich-Soeldner, Roland
Wedlich-Söldner, Roland / Cellular Dynamics and Cell Patterning, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons38775

Bradke, Frank
Max Planck Research Group: Axonal Growth and Regeneration / Bradke, MPI of Neurobiology, Max Planck Society;

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Citation

Flynn, K. C., Hellal, F., Neukirchen, D., Jacob, S., Tahirovic, S., Dupraz, S., et al. (2012). ADF/Cofilin-Mediated Actin Retrograde Flow Directs Neurite Formation in the Developing Brain. NEURON, 76(6), 1091-1107. doi:10.1016/j.neuron.2012.09.038.

Cite as: https://hdl.handle.net/11858/00-001M-0000-000E-8B90-8

Abstract

Neurites are the characteristic structural element of neurons that will initiate brain connectivity and elaborate information. Early in development, neurons are spherical cells but this symmetry is broken through the initial formation of neurites. This fundamental step is thought to rely on actin and microtubule dynamics. However, it is unclear which aspects of the complex actin behavior control neuritogenesis and which molecular mechanisms are involved. Here, we demonstrate that augmented actin retrograde flow and protrusion dynamics facilitate neurite formation. Our data indicate that a single family of actin regulatory proteins, ADF/Cofilin, provides the required control of actin retrograde flow and dynamics to form neurites. In particular, the F-actin severing activity of ADF/Cofilin organizes space for the protrusion and bundling of microtubules, the backbone of neurites. Our data reveal how ADF/Cofilin organizes the cytoskeleton to drive actin retrograde flow and thus break the spherical shape of neurons.