---
_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. Nature Communications. 2021;12.
doi:10.1038/s41467-021-27135-5
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. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-021-27135-5
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.” Nature Communications.
Springer Nature, 2021. https://doi.org/10.1038/s41467-021-27135-5.
ieee: M. C. Ucar et al., “Theory of branching morphogenesis by local interactions
and global guidance,” Nature Communications, 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.” Nature Communications, vol. 12, 6830, Springer Nature,
2021, doi:10.1038/s41467-021-27135-5.
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:
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creator: cchlebak
date_created: 2021-12-10T08:54:09Z
date_updated: 2021-12-10T08:54:09Z
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relation: main_file
success: 1
file_date_updated: 2021-12-10T08:54:09Z
has_accepted_license: '1'
intvolume: ' 12'
isi: 1
language:
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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
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...