---
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
file:
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  creator: dernst
  date_created: 2026-05-04T09:16:36Z
  date_updated: 2026-05-04T09:16:36Z
  file_id: '21786'
  file_name: 2026_ScienceAdv_Markovitsch.pdf
  file_size: 11101140
  relation: main_file
  success: 1
file_date_updated: 2026-05-04T09:16:36Z
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)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 12
year: '2026'
...
---
APC_amount: 5766,07 EUR
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '20289'
abstract:
- lang: eng
  text: Cell and tissue movement in development, cancer invasion, and immune response
    relies on chemical or mechanical guidance cues. In many systems, this behavior
    is locally directed by self-generated signaling gradients rather than long-range,
    prepatterned cues. However, how heterogeneous mixtures of cells interact nonreciprocally
    and navigate through self-generated gradients remains largely unexplored. Here,
    we introduce a theoretical framework for the self-organized chemotaxis of heterogeneous
    cell populations. We find that the relative chemotactic sensitivities of different
    cell populations control their long-time coupling and comigration dynamics, with
    boundary conditions such as external cell and attractant reservoirs substantially
    influencing the migration patterns. Our model predicts an optimal parameter regime
    that enables robust and colocalized migration. We test our theoretical predictions
    with in vitro experiments demonstrating the comigration of distinct immune cell
    populations, and quantitatively reproduce observed migration patterns under wild-type
    and perturbed conditions. Interestingly, immune cell comigration occurs close
    to the predicted optimal regime. Finally, we incorporate mechanical interactions
    into our framework, revealing a nontrivial interplay between chemotactic and mechanical
    nonreciprocity in driving collective migration. Together, our findings suggest
    that self-generated chemotaxis is a robust strategy for the navigation of mixed
    cell populations.
acknowledged_ssus:
- _id: Bio
- _id: PreCl
- _id: LifeSc
- _id: NanoFab
acknowledgement: We thank all members of the M.S. and E.H. groups for stimulating
  discussions.We thank the Imaging and Optics facility, the Pre-clinical and Lab Support
  facility of the Institute of Science and Technology Austria for their excellent
  support and provided resources for the experimental research. In particular, we
  thank Jack Merrin from the Nanofabrication facility who generated the microfabricated
  channel used in this study. This work received funding fromt he European Research
  Council under the European Union’s Horizon 2020 research and innovation program
  (grant agreement No. 851288 to E.H.). M.C.U.is funded by a University of Sheffield
  Strategic Research Fellowship in the Physics of Life and Quantitative Biology.
article_number: e2504064122
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Mehmet C
  full_name: Ucar, Mehmet C
  id: 50B2A802-6007-11E9-A42B-EB23E6697425
  last_name: Ucar
  orcid: 0000-0003-0506-4217
- first_name: Alsberga
  full_name: Zane, Alsberga
  id: 60f7509a-f652-11ea-9d86-b963d6490d7c
  last_name: Zane
  orcid: 0009-0003-0415-7603
- first_name: Jonna H
  full_name: Alanko, Jonna H
  id: 2CC12E8C-F248-11E8-B48F-1D18A9856A87
  last_name: Alanko
  orcid: 0000-0002-7698-3061
- first_name: Michael K
  full_name: Sixt, Michael K
  id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
  last_name: Sixt
  orcid: 0000-0002-6620-9179
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
citation:
  ama: Ucar MC, Zane A, Alanko JH, Sixt MK, Hannezo EB. Self-generated chemotaxis
    of mixed cell populations. <i>Proceedings of the National Academy of Sciences</i>.
    2025;122(34). doi:<a href="https://doi.org/10.1073/pnas.2504064122">10.1073/pnas.2504064122</a>
  apa: Ucar, M. C., Zane, A., Alanko, J. H., Sixt, M. K., &#38; Hannezo, E. B. (2025).
    Self-generated chemotaxis of mixed cell populations. <i>Proceedings of the National
    Academy of Sciences</i>. National Academy of Sciences. <a href="https://doi.org/10.1073/pnas.2504064122">https://doi.org/10.1073/pnas.2504064122</a>
  chicago: Ucar, Mehmet C, Alsberga Zane, Jonna H Alanko, Michael K Sixt, and Edouard
    B Hannezo. “Self-Generated Chemotaxis of Mixed Cell Populations.” <i>Proceedings
    of the National Academy of Sciences</i>. National Academy of Sciences, 2025. <a
    href="https://doi.org/10.1073/pnas.2504064122">https://doi.org/10.1073/pnas.2504064122</a>.
  ieee: M. C. Ucar, A. Zane, J. H. Alanko, M. K. Sixt, and E. B. Hannezo, “Self-generated
    chemotaxis of mixed cell populations,” <i>Proceedings of the National Academy
    of Sciences</i>, vol. 122, no. 34. National Academy of Sciences, 2025.
  ista: Ucar MC, Zane A, Alanko JH, Sixt MK, Hannezo EB. 2025. Self-generated chemotaxis
    of mixed cell populations. Proceedings of the National Academy of Sciences. 122(34),
    e2504064122.
  mla: Ucar, Mehmet C., et al. “Self-Generated Chemotaxis of Mixed Cell Populations.”
    <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 34, e2504064122,
    National Academy of Sciences, 2025, doi:<a href="https://doi.org/10.1073/pnas.2504064122">10.1073/pnas.2504064122</a>.
  short: M.C. Ucar, A. Zane, J.H. Alanko, M.K. Sixt, E.B. Hannezo, Proceedings of
    the National Academy of Sciences 122 (2025).
corr_author: '1'
date_created: 2025-09-07T22:01:32Z
date_published: 2025-08-26T00:00:00Z
date_updated: 2026-05-20T08:59:54Z
day: '26'
ddc:
- '570'
department:
- _id: EdHa
- _id: MiSi
doi: 10.1073/pnas.2504064122
ec_funded: 1
external_id:
  isi:
  - '001562181600001'
  pmid:
  - '40838890'
file:
- access_level: open_access
  checksum: b36abd92673b6d76376fc9434bad52cc
  content_type: application/pdf
  creator: dernst
  date_created: 2025-09-08T07:23:29Z
  date_updated: 2025-09-08T07:23:29Z
  file_id: '20307'
  file_name: 2025_PNAS_Ucar.pdf
  file_size: 16069140
  relation: main_file
  success: 1
file_date_updated: 2025-09-08T07:23:29Z
has_accepted_license: '1'
intvolume: '       122'
isi: 1
issue: '34'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
  call_identifier: H2020
  grant_number: '851288'
  name: Design Principles of Branching Morphogenesis
publication: Proceedings of the National Academy of Sciences
publication_identifier:
  eissn:
  - 1091-6490
  issn:
  - 0027-8424
publication_status: published
publisher: National Academy of Sciences
quality_controlled: '1'
related_material:
  link:
  - relation: software
    url: https://github.com/mehmetcanucar/Self-generated-chemotaxis
scopus_import: '1'
status: public
title: Self-generated chemotaxis of mixed cell populations
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
volume: 122
year: '2025'
...