---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
_id: '21707'
abstract:
- lang: eng
  text: Structural and functional differences between brain hemispheres are a common
    feature of animal nervous systems with reduced bilateral asymmetry often linked
    to impaired cognitive performance. How neuronal left-right asymmetry is initiated
    and integrated into a bilaterally symmetrical ground pattern is poorly understood.
    Here, we show that the directional asymmetry of a Drosophila central brain circuit
    originates from axonal interactions of two types of bilateral pioneer neurons.
    Subsequent recruitment of neighboring neurons into the asymmetric neuropil primordium
    results in hemisphere-specific microcircuits. Circuit lateralization requires
    dynamic expression of the cell adhesion molecule Fasciclin 2 to maintain structural
    plasticity in axonal remodeling. Reduced circuit asymmetry following cell type–specific
    Fasciclin 2 manipulation affects adult brain function. These results reveal an
    unexpected degree of developmental plasticity of late-born Drosophila neurons
    in the formation of a circuit node via the lateralized recruitment of symmetric
    circuit components.
acknowledgement: "We thank I. Salecker (Flybow), B. Altenhein (Fas2-Gal4Mz507), A.
  Nose (UAS-intra- and extra-Fas2::YFP), and C. S. Goodman (UAS-Fas2PEST+/−), as well
  as the Bloomington Stock Center for providing materials and fly stocks. We thank
  S. Waddell and the lab, especially B. Senapati, for providing the opportunity to
  conduct memory experiments at the CNCB, University of Oxford, and for supervision
  and discussions during this period. We also thank W. Kallina, S. Ilgerl, D. Bartel,
  A. Grimm, and A. Litin for technical support and the Hummel Lab for stimulating
  discussions and critical comments on the manuscript. We acknowledge the early exploratory
  work of A. Mattia, S. Trkulja, C. Schönherr, S. Bogner, B. Simpson, L. Tomasek,
  H. Roth, H. Vokač, R. Gredler, F. Kapelari, T. Kolarova, C. Ignitsch, Á. Bautista-Soldevila,
  and M. Kassem.\r\nThis research was funded by the University of Vienna, the Vienna
  Doctoral School Cognition, Behaviour and Neuroscience (uni:docs fellowship) (to
  J.W.M.) and by the Austrian Science Fund (FWF) (Cluster of Excellence Neuronal Circuits
  in Health and Disease, grant DOI 10.55776/COE16; https://www.fwf.ac.at/en/research-radar/10.55776/COE16)
  (to T.H.). For open access purposes, the author has applied a CC BY public copyright
  license to any author-accepted manuscript version arising from this submission."
article_number: eaea6020
article_processing_charge: Yes
article_type: original
author:
- first_name: Johann W.
  full_name: Markovitsch, Johann W.
  last_name: Markovitsch
- first_name: Daniel
  full_name: Mitić, Daniel
  last_name: Mitić
- first_name: Alisa
  full_name: Del Pilar Jiménez García, Alisa
  last_name: Del Pilar Jiménez García
- first_name: Alsberga
  full_name: Zane, Alsberga
  id: 60f7509a-f652-11ea-9d86-b963d6490d7c
  last_name: Zane
  orcid: 0009-0003-0415-7603
- first_name: Sarah
  full_name: Kainz, Sarah
  last_name: Kainz
- first_name: Rashmit
  full_name: Kaur, Rashmit
  last_name: Kaur
- first_name: Thomas
  full_name: Hummel, Thomas
  last_name: Hummel
citation:
  ama: Markovitsch JW, Mitić D, Del Pilar Jiménez García A, et al. Sequential formation
    of Drosophila circuit asymmetry via prolonged structural plasticity. <i>Science
    Advances</i>. 2026;12(13). doi:<a href="https://doi.org/10.1126/sciadv.aea6020">10.1126/sciadv.aea6020</a>
  apa: Markovitsch, J. W., Mitić, D., Del Pilar Jiménez García, A., Zane, A., Kainz,
    S., Kaur, R., &#38; Hummel, T. (2026). Sequential formation of Drosophila circuit
    asymmetry via prolonged structural plasticity. <i>Science Advances</i>. American
    Association for the Advancement of Science. <a href="https://doi.org/10.1126/sciadv.aea6020">https://doi.org/10.1126/sciadv.aea6020</a>
  chicago: Markovitsch, Johann W., Daniel Mitić, Alisa Del Pilar Jiménez García, Alsberga
    Zane, Sarah Kainz, Rashmit Kaur, and Thomas Hummel. “Sequential Formation of Drosophila
    Circuit Asymmetry via Prolonged Structural Plasticity.” <i>Science Advances</i>.
    American Association for the Advancement of Science, 2026. <a href="https://doi.org/10.1126/sciadv.aea6020">https://doi.org/10.1126/sciadv.aea6020</a>.
  ieee: J. W. Markovitsch <i>et al.</i>, “Sequential formation of Drosophila circuit
    asymmetry via prolonged structural plasticity,” <i>Science Advances</i>, vol.
    12, no. 13. American Association for the Advancement of Science, 2026.
  ista: Markovitsch JW, Mitić D, Del Pilar Jiménez García A, Zane A, Kainz S, Kaur
    R, Hummel T. 2026. Sequential formation of Drosophila circuit asymmetry via prolonged
    structural plasticity. Science Advances. 12(13), eaea6020.
  mla: Markovitsch, Johann W., et al. “Sequential Formation of Drosophila Circuit
    Asymmetry via Prolonged Structural Plasticity.” <i>Science Advances</i>, vol.
    12, no. 13, eaea6020, American Association for the Advancement of Science, 2026,
    doi:<a href="https://doi.org/10.1126/sciadv.aea6020">10.1126/sciadv.aea6020</a>.
  short: J.W. Markovitsch, D. Mitić, A. Del Pilar Jiménez García, A. Zane, S. Kainz,
    R. Kaur, T. Hummel, Science Advances 12 (2026).
date_created: 2026-04-12T22:01:48Z
date_published: 2026-03-27T00:00:00Z
date_updated: 2026-05-04T09:18:06Z
day: '27'
ddc:
- '570'
department:
- _id: MiSi
- _id: GradSch
doi: 10.1126/sciadv.aea6020
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has_accepted_license: '1'
intvolume: '        12'
issue: '13'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
publication: Science Advances
publication_identifier:
  eissn:
  - 2375-2548
publication_status: published
publisher: American Association for the Advancement of Science
quality_controlled: '1'
scopus_import: '1'
status: public
title: Sequential formation of Drosophila circuit asymmetry via prolonged structural
  plasticity
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)
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type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
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