An intrinsic cytoskeletal oscillator establishes neuronal polarity
11 affiliations
- 1Laboratory for Axon Growth and Regeneration, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
- 2Biopharm Discovery, GlaxoSmithKline, Stevenage, UK
- 3Department of Integrated Structural Biology, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France
- 4Institute of Science and Technology Austria (ISTA), Klosterneuburg, Austria
- 5International Max Planck Research School for Brain and Behavior, Bonn, Germany
- 6Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya, Japan
- 7CaseBioscience, Woodbury, MN, USA
- 8Image and Data Analysis Facility, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
- 9International Collaboration on Repair Discoveries (ICORD), Djavad Mowafaghian Centre for Brain Health, and Department of Cellular and Physiological Sciences, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
- 10Department of Cellular and Molecular Neurobiology, Technische Universität Braunschweig, Braunschweig, Germany
- 11Laboratory for Axon Growth and Regeneration, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany. [email protected]
Abstract
Neurons acquire polarity by specifying one neurite as the axon, whereas the others become dendrites. But how this fundamental asymmetry is established remains unclear 1 . Neuronal polarization has been thought to rely primarily on growth cones that sense external cues 2 . Here we show that growth cones alone do not direct this process and that the soma acts as a central organizer of neuronal polarization. Using live imaging and genetic loss-of-function approaches in vivo, combined with optogenetic control and local cytoskeletal perturbations in cultured neurons, we uncover a soma-initiated oscillatory program that primes axon selection. Periodic actin branching that depends on the actin-related protein 2/3 (ARP2/3) complex at the soma remodels a global actomyosin network, thereby generating an actin wave that retracts neurites before propagating into a single neurite tip. Exposure to this wave relaxes local actomyosin contractility, which drives a transient microtubule-based protrusion and biases this neurite towards axon fate. As the cell exits this oscillatory stage, this neurite can overcome global inhibition and extend independently of ARP2/3, whereas actomyosin activity suppresses axon formation in the remaining neurites so that they subsequently become dendrites. This soma-driven mechanism ensures the emergence of a single axon independent of environmental cues and underpins the unidirectional information flow in neuronal circuits.
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BibTeX
@article{lin2026intrinsic,
title = {{An intrinsic cytoskeletal oscillator establishes neuronal polarity}},
author = {Tien-chen Lin and Charlotte H. Coles and Eissa Alfadil and Florian Fäßler and Andreas Husch and Sebastián Dupraz and Thorben Pietralla and Akihiro Narita and Max Schelski and Kevin C. Flynn and Sina Stern and Christoph Möhl and Brett J. Hilton and Franz Vauti and Arnold Hh and Florian K. M. Schur and Frank Bradke},
journal = {Nature},
year = {2026},
month = jul,
doi = {10.1038/s41586-026-10755-6},
url = {https://doi.org/10.1038/s41586-026-10755-6},
note = {CC BY},
}
RIS
TY - JOUR
TI - An intrinsic cytoskeletal oscillator establishes neuronal polarity
AU - Tien-chen Lin
AU - Charlotte H. Coles
AU - Eissa Alfadil
AU - Florian Fäßler
AU - Andreas Husch
AU - Sebastián Dupraz
AU - Thorben Pietralla
AU - Akihiro Narita
AU - Max Schelski
AU - Kevin C. Flynn
AU - Sina Stern
AU - Christoph Möhl
AU - Brett J. Hilton
AU - Franz Vauti
AU - Arnold Hh
AU - Florian K. M. Schur
AU - Frank Bradke
PY - 2026
DA - 2026/07/08
JO - Nature
DO - 10.1038/s41586-026-10755-6
UR - https://doi.org/10.1038/s41586-026-10755-6
AB - Neurons acquire polarity by specifying one neurite as the axon, whereas the others become dendrites. But how this fundamental asymmetry is established remains unclear 1 . Neuronal polarization has been thought to rely primarily on growth cones that sense external cues 2 . Here we show that growth cones alone do not direct this process and that the soma acts as a central organizer of neuronal polarization. Using live imaging and genetic loss-of-function approaches in vivo, combined with optogenetic control and local cytoskeletal perturbations in cultured neurons, we uncover a soma-initiated oscillatory program that primes axon selection. Periodic actin branching that depends on the actin-related protein 2/3 (ARP2/3) complex at the soma remodels a global actomyosin network, thereby generating an actin wave that retracts neurites before propagating into a single neurite tip. Exposure to this wave relaxes local actomyosin contractility, which drives a transient microtubule-based protrusion and biases this neurite towards axon fate. As the cell exits this oscillatory stage, this neurite can overcome global inhibition and extend independently of ARP2/3, whereas actomyosin activity suppresses axon formation in the remaining neurites so that they subsequently become dendrites. This soma-driven mechanism ensures the emergence of a single axon independent of environmental cues and underpins the unidirectional information flow in neuronal circuits.
SN - 0028-0836
SN - 1476-4687
ER -