---
_id: '10402'
abstract:
- lang: eng
  text: Branching morphogenesis governs the formation of many organs such as lung,
    kidney, and the neurovascular system. Many studies have explored system-specific
    molecular and cellular regulatory mechanisms, as well as self-organizing rules
    underlying branching morphogenesis. However, in addition to local cues, branched
    tissue growth can also be influenced by global guidance. Here, we develop a theoretical
    framework for a stochastic self-organized branching process in the presence of
    external cues. Combining analytical theory with numerical simulations, we predict
    differential signatures of global vs. local regulatory mechanisms on the branching
    pattern, such as angle distributions, domain size, and space-filling efficiency.
    We find that branch alignment follows a generic scaling law determined by the
    strength of global guidance, while local interactions influence the tissue density
    but not its overall territory. Finally, using zebrafish innervation as a model
    system, we test these key features of the model experimentally. Our work thus
    provides quantitative predictions to disentangle the role of different types of
    cues in shaping branched structures across scales.
acknowledgement: We thank all members of our respective groups for helpful discussion
  on the paper. The authors are also grateful to Prof. Abdel El. Manira for support
  and sharing Tg(HUC:Gal4;UAS:Synaptohysin-GFP), to Haohao Wu for discussion, and
  thank Elena Zabalueva for the zebrafish schematic. The authors also acknowledge
  Zebrafish core facility, Genome Engineering Zebrafish and Biomedicum Imaging Core
  from the Karolinska Institutet for technical support. This work received funding
  from the ERC under the European Union’s Horizon 2020 research and innovation programme
  (grant agreement No. 851288 to E.H.) and under the Marie Skłodowska-Curie grant
  agreement No. 754411 (to M.C.U.); Swedish Research Council (to F.L., I.A. and S.H.);
  Knut and Alice Wallenberg Foundation (F.L. and I.A.); Swedish Brain Foundation (F.L.
  and S.H.); Ming Wai Lau Foundation (to F.L.); StratRegen (to F.L.); ERC Consolidator
  grant STEMMING-FROM-NERVE and ERC Synergy Grant KILL-OR-DIFFERENTIATE (to I.A.);
  Bertil Hallsten Research Foundation (to I.A.); Cancerfonden (to I.A.); the Paradifference
  Foundation (to I.A.); Austrian Science Fund (to I.A.); and StratNeuro (to S.H.).
article_number: '6830'
article_processing_charge: No
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: Dmitrii
  full_name: Kamenev, Dmitrii
  last_name: Kamenev
- first_name: Kazunori
  full_name: Sunadome, Kazunori
  last_name: Sunadome
- first_name: Dominik C
  full_name: Fachet, Dominik C
  id: 14FDD550-AA41-11E9-A0E5-1ACCE5697425
  last_name: Fachet
- first_name: Francois
  full_name: Lallemend, Francois
  last_name: Lallemend
- first_name: Igor
  full_name: Adameyko, Igor
  last_name: Adameyko
- first_name: Saida
  full_name: Hadjab, Saida
  last_name: Hadjab
- 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, Kamenev D, Sunadome K, et al. Theory of branching morphogenesis by
    local interactions and global guidance. <i>Nature Communications</i>. 2021;12.
    doi:<a href="https://doi.org/10.1038/s41467-021-27135-5">10.1038/s41467-021-27135-5</a>
  apa: Ucar, M. C., Kamenev, D., Sunadome, K., Fachet, D. C., Lallemend, F., Adameyko,
    I., … Hannezo, E. B. (2021). Theory of branching morphogenesis by local interactions
    and global guidance. <i>Nature Communications</i>. Springer Nature. <a href="https://doi.org/10.1038/s41467-021-27135-5">https://doi.org/10.1038/s41467-021-27135-5</a>
  chicago: Ucar, Mehmet C, Dmitrii Kamenev, Kazunori Sunadome, Dominik C Fachet, Francois
    Lallemend, Igor Adameyko, Saida Hadjab, and Edouard B Hannezo. “Theory of Branching
    Morphogenesis by Local Interactions and Global Guidance.” <i>Nature Communications</i>.
    Springer Nature, 2021. <a href="https://doi.org/10.1038/s41467-021-27135-5">https://doi.org/10.1038/s41467-021-27135-5</a>.
  ieee: M. C. Ucar <i>et al.</i>, “Theory of branching morphogenesis by local interactions
    and global guidance,” <i>Nature Communications</i>, vol. 12. Springer Nature,
    2021.
  ista: Ucar MC, Kamenev D, Sunadome K, Fachet DC, Lallemend F, Adameyko I, Hadjab
    S, Hannezo EB. 2021. Theory of branching morphogenesis by local interactions and
    global guidance. Nature Communications. 12, 6830.
  mla: Ucar, Mehmet C., et al. “Theory of Branching Morphogenesis by Local Interactions
    and Global Guidance.” <i>Nature Communications</i>, vol. 12, 6830, Springer Nature,
    2021, doi:<a href="https://doi.org/10.1038/s41467-021-27135-5">10.1038/s41467-021-27135-5</a>.
  short: M.C. Ucar, D. Kamenev, K. Sunadome, D.C. Fachet, F. Lallemend, I. Adameyko,
    S. Hadjab, E.B. Hannezo, Nature Communications 12 (2021).
date_created: 2021-12-05T23:01:40Z
date_published: 2021-11-24T00:00:00Z
date_updated: 2023-08-14T13:18:46Z
day: '24'
ddc:
- '573'
department:
- _id: EdHa
doi: 10.1038/s41467-021-27135-5
ec_funded: 1
external_id:
  isi:
  - '000722322900020'
  pmid:
  - '34819507'
file:
- access_level: open_access
  checksum: 63c56ec75314a71e63e7dd2920b3c5b5
  content_type: application/pdf
  creator: cchlebak
  date_created: 2021-12-10T08:54:09Z
  date_updated: 2021-12-10T08:54:09Z
  file_id: '10529'
  file_name: 2021_NatComm_Ucar.pdf
  file_size: 2303405
  relation: main_file
  success: 1
file_date_updated: 2021-12-10T08:54:09Z
has_accepted_license: '1'
intvolume: '        12'
isi: 1
language:
- iso: eng
month: '11'
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
- _id: 260C2330-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '754411'
  name: ISTplus - Postdoctoral Fellowships
publication: Nature Communications
publication_identifier:
  eissn:
  - 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
  record:
  - id: '13058'
    relation: research_data
    status: public
scopus_import: '1'
status: public
title: Theory of branching morphogenesis by local interactions and global guidance
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: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 12
year: '2021'
...