---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '22372'
abstract:
- lang: eng
  text: Neurons acquire polarity by specifying one neurite as the axon, whereas the
    others become dendrites. But how this fundamental asymmetry is established remains
    unclear1. Neuronal polarization has been thought to rely primarily on growth cones
    that sense external cues2. 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.
acknowledgement: 'We thank O. Gruss, E. Handley, H. Herzel, A. Kania, A. Koseska,
  E. Kiermaier, D. Manstein, C. Niessen, K. Rottner, J. Schiweck, G. Tavosanis, D. Wachten,
  R. Wedlich-Söldner and W. Witke for critically reading and discussing the manuscript;
  C. Günter and V. Štimac for feedback on data presentation; B. Randel, J. Benner,
  L. Meyn and A.-T. Pham for technical assistance; L. M. Neußer, K. Herz, K. Van-De-Kamp
  and M. Diwo for their support on mice maintenance; H. Fried, I. Koenig, S. Filser
  and Y. Fu for their technical support on experimental setup; and M. Aghabeig for
  writing the Fiji macro scripts. C.H.C. was a Human Frontier Science Program Long-term
  Postdoctoral Fellow (LT000100/2013). F.B. is supported by the Deutsches Zentrum
  für Neurodegenerative Erkrankungen (DZNE), the International Foundation for Research
  in Paraplegia, Wings for Life, ERANET AXON REPAIR, ERANET RATER SCI and the Chan–Zuckerberg
  Initiative (CZI). F.B. is also funded by the Deutsche Forschungsgemeinschaft (DFG,
  German Research Foundation)–Project-ID 227953431–SFB 1089, SFB 1690 as well as SFB
  1158 and SPP 2395. F.B. is a member of the excellence cluster ImmunoSensation2 (EXC2151–390873048)
  and the iBehave NRW network. F.B. is a recipient of the Roger de Spoelberch Prize.
  F.K.M.S. acknowledges support from Austrian Science Fund (FWF): P33367. A.N. is
  supported by JSPS KAKENHI (grant numbers 18H02410 and 21H02440). Open access funding
  provided by Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. (DZNE) in
  der Helmholtz-Gemeinschaft.'
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Tien Chen
  full_name: Lin, Tien Chen
  last_name: Lin
- first_name: Charlotte H.
  full_name: Coles, Charlotte H.
  last_name: Coles
- first_name: Eissa
  full_name: Alfadil, Eissa
  last_name: Alfadil
- first_name: Florian
  full_name: Fäßler, Florian
  id: 404F5528-F248-11E8-B48F-1D18A9856A87
  last_name: Fäßler
  orcid: 0000-0001-7149-769X
- first_name: Andreas
  full_name: Husch, Andreas
  last_name: Husch
- first_name: Sebastian
  full_name: Dupraz, Sebastian
  last_name: Dupraz
- first_name: Thorben
  full_name: Pietralla, Thorben
  last_name: Pietralla
- first_name: Akihiro
  full_name: Narita, Akihiro
  last_name: Narita
- first_name: Max
  full_name: Schelski, Max
  last_name: Schelski
- first_name: Kevin C.
  full_name: Flynn, Kevin C.
  last_name: Flynn
- first_name: Sina
  full_name: Stern, Sina
  last_name: Stern
- first_name: Christoph
  full_name: Möhl, Christoph
  last_name: Möhl
- first_name: Brett J.
  full_name: Hilton, Brett J.
  last_name: Hilton
- first_name: Franz
  full_name: Vauti, Franz
  last_name: Vauti
- first_name: Hans Henning
  full_name: Arnold, Hans Henning
  last_name: Arnold
- first_name: Florian Km
  full_name: Schur, Florian Km
  id: 48AD8942-F248-11E8-B48F-1D18A9856A87
  last_name: Schur
  orcid: 0000-0003-4790-8078
- first_name: Frank
  full_name: Bradke, Frank
  last_name: Bradke
citation:
  ama: Lin TC, Coles CH, Alfadil E, et al. An intrinsic cytoskeletal oscillator establishes
    neuronal polarity. <i>Nature</i>. 2026. doi:<a href="https://doi.org/10.1038/s41586-026-10755-6">10.1038/s41586-026-10755-6</a>
  apa: Lin, T. C., Coles, C. H., Alfadil, E., Fäßler, F., Husch, A., Dupraz, S., …
    Bradke, F. (2026). An intrinsic cytoskeletal oscillator establishes neuronal polarity.
    <i>Nature</i>. Springer Nature. <a href="https://doi.org/10.1038/s41586-026-10755-6">https://doi.org/10.1038/s41586-026-10755-6</a>
  chicago: Lin, Tien Chen, Charlotte H. Coles, Eissa Alfadil, Florian Fäßler, Andreas
    Husch, Sebastian Dupraz, Thorben Pietralla, et al. “An Intrinsic Cytoskeletal
    Oscillator Establishes Neuronal Polarity.” <i>Nature</i>. Springer Nature, 2026.
    <a href="https://doi.org/10.1038/s41586-026-10755-6">https://doi.org/10.1038/s41586-026-10755-6</a>.
  ieee: T. C. Lin <i>et al.</i>, “An intrinsic cytoskeletal oscillator establishes
    neuronal polarity,” <i>Nature</i>. Springer Nature, 2026.
  ista: Lin TC, Coles CH, Alfadil E, Fäßler F, Husch A, Dupraz S, Pietralla T, Narita
    A, Schelski M, Flynn KC, Stern S, Möhl C, Hilton BJ, Vauti F, Arnold HH, Schur
    FK, Bradke F. 2026. An intrinsic cytoskeletal oscillator establishes neuronal
    polarity. Nature.
  mla: Lin, Tien Chen, et al. “An Intrinsic Cytoskeletal Oscillator Establishes Neuronal
    Polarity.” <i>Nature</i>, Springer Nature, 2026, doi:<a href="https://doi.org/10.1038/s41586-026-10755-6">10.1038/s41586-026-10755-6</a>.
  short: T.C. Lin, C.H. Coles, E. Alfadil, F. Fäßler, A. Husch, S. Dupraz, T. Pietralla,
    A. Narita, M. Schelski, K.C. Flynn, S. Stern, C. Möhl, B.J. Hilton, F. Vauti,
    H.H. Arnold, F.K. Schur, F. Bradke, Nature (2026).
das_tickbox: '1'
dataavailabilitystatement: The raw data of the representative images have been deposited
  into Zenodo (https://doi.org/10.5281/zenodo.20118606)99. Owing to the large file
  size of the raw image data and the processed data used in the analyses that generated
  the graphs, we archived the image files in the read-only file archive at the DZNE
  institute. We provide raw data files upon request. The request can be directed to
  and will be fulfilled by the lead contact F.B. Source data are provided with this
  paper. The custom ImageJ macro used for generating kymographs, extracting neurite
  tip positions and protein intensities is available at GitHub (https://github.com/darkbreaker0/IJ_NeuriteGrowthScript)
  and Zenodo (https://doi.org/10.5281/zenodo.20118606)99. The custom R and Python
  scripts used in the study are available at GitHub (https://github.com/darkbreaker0/Arp3_neuronal_polarization_2026)
  and Zenodo (https://doi.org/10.5281/zenodo.20118606)99. The code used for polarity
  determination of the actin filament in tomograms is available at Zenodo (https://doi.org/10.5281/zenodo.20081075)93.
date_created: 2026-07-19T22:01:48Z
date_published: 2026-07-08T00:00:00Z
date_updated: 2026-07-20T14:18:10Z
day: '08'
ddc:
- '570'
department:
- _id: FlSc
doi: 10.1038/s41586-026-10755-6
external_id:
  pmid:
  - '42420447'
has_accepted_license: '1'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1038/s41586-026-10755-6
month: '07'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 9B954C5C-BA93-11EA-9121-9846C619BF3A
  grant_number: P33367
  name: Structure and isoform diversity of the Arp2/3 complex
publication: Nature
publication_identifier:
  eissn:
  - 1476-4687
  issn:
  - 0028-0836
publication_status: epub_ahead
publisher: Springer Nature
quality_controlled: '1'
researchdata_availability: yes
scopus_import: '1'
status: public
supplementarymaterial: yes
title: An intrinsic cytoskeletal oscillator establishes neuronal polarity
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2026'
...