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Self-organized and directed branching results in optimal coverage in developing dermal lymphatic networks

Branching morphogenesis is a ubiquitous process that gives rise to high exchange surfaces in the vasculature and epithelial organs. Lymphatic capillaries form branched networks, which play a key role in the circulation of tissue fluid and immune cells. Although mouse models and correlative patient d...

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Autores principales: Uçar, Mehmet Can, Hannezo, Edouard, Tiilikainen, Emmi, Liaqat, Inam, Jakobsson, Emma, Nurmi, Harri, Vaahtomeri, Kari
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10514270/
https://www.ncbi.nlm.nih.gov/pubmed/37735168
http://dx.doi.org/10.1038/s41467-023-41456-7
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author Uçar, Mehmet Can
Hannezo, Edouard
Tiilikainen, Emmi
Liaqat, Inam
Jakobsson, Emma
Nurmi, Harri
Vaahtomeri, Kari
author_facet Uçar, Mehmet Can
Hannezo, Edouard
Tiilikainen, Emmi
Liaqat, Inam
Jakobsson, Emma
Nurmi, Harri
Vaahtomeri, Kari
author_sort Uçar, Mehmet Can
collection PubMed
description Branching morphogenesis is a ubiquitous process that gives rise to high exchange surfaces in the vasculature and epithelial organs. Lymphatic capillaries form branched networks, which play a key role in the circulation of tissue fluid and immune cells. Although mouse models and correlative patient data indicate that the lymphatic capillary density directly correlates with functional output, i.e., tissue fluid drainage and trafficking efficiency of dendritic cells, the mechanisms ensuring efficient tissue coverage remain poorly understood. Here, we use the mouse ear pinna lymphatic vessel network as a model system and combine lineage-tracing, genetic perturbations, whole-organ reconstructions and theoretical modeling to show that the dermal lymphatic capillaries tile space in an optimal, space-filling manner. This coverage is achieved by two complementary mechanisms: initial tissue invasion provides a non-optimal global scaffold via self-organized branching morphogenesis, while VEGF-C dependent side-branching from existing capillaries rapidly optimizes local coverage by directionally targeting low-density regions. With these two ingredients, we show that a minimal biophysical model can reproduce quantitatively whole-network reconstructions, across development and perturbations. Our results show that lymphatic capillary networks can exploit local self-organizing mechanisms to achieve tissue-scale optimization.
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spelling pubmed-105142702023-09-23 Self-organized and directed branching results in optimal coverage in developing dermal lymphatic networks Uçar, Mehmet Can Hannezo, Edouard Tiilikainen, Emmi Liaqat, Inam Jakobsson, Emma Nurmi, Harri Vaahtomeri, Kari Nat Commun Article Branching morphogenesis is a ubiquitous process that gives rise to high exchange surfaces in the vasculature and epithelial organs. Lymphatic capillaries form branched networks, which play a key role in the circulation of tissue fluid and immune cells. Although mouse models and correlative patient data indicate that the lymphatic capillary density directly correlates with functional output, i.e., tissue fluid drainage and trafficking efficiency of dendritic cells, the mechanisms ensuring efficient tissue coverage remain poorly understood. Here, we use the mouse ear pinna lymphatic vessel network as a model system and combine lineage-tracing, genetic perturbations, whole-organ reconstructions and theoretical modeling to show that the dermal lymphatic capillaries tile space in an optimal, space-filling manner. This coverage is achieved by two complementary mechanisms: initial tissue invasion provides a non-optimal global scaffold via self-organized branching morphogenesis, while VEGF-C dependent side-branching from existing capillaries rapidly optimizes local coverage by directionally targeting low-density regions. With these two ingredients, we show that a minimal biophysical model can reproduce quantitatively whole-network reconstructions, across development and perturbations. Our results show that lymphatic capillary networks can exploit local self-organizing mechanisms to achieve tissue-scale optimization. Nature Publishing Group UK 2023-09-21 /pmc/articles/PMC10514270/ /pubmed/37735168 http://dx.doi.org/10.1038/s41467-023-41456-7 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Uçar, Mehmet Can
Hannezo, Edouard
Tiilikainen, Emmi
Liaqat, Inam
Jakobsson, Emma
Nurmi, Harri
Vaahtomeri, Kari
Self-organized and directed branching results in optimal coverage in developing dermal lymphatic networks
title Self-organized and directed branching results in optimal coverage in developing dermal lymphatic networks
title_full Self-organized and directed branching results in optimal coverage in developing dermal lymphatic networks
title_fullStr Self-organized and directed branching results in optimal coverage in developing dermal lymphatic networks
title_full_unstemmed Self-organized and directed branching results in optimal coverage in developing dermal lymphatic networks
title_short Self-organized and directed branching results in optimal coverage in developing dermal lymphatic networks
title_sort self-organized and directed branching results in optimal coverage in developing dermal lymphatic networks
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10514270/
https://www.ncbi.nlm.nih.gov/pubmed/37735168
http://dx.doi.org/10.1038/s41467-023-41456-7
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