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

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  • Mehmet Can Uçar

    (Institute of Science and Technology Austria (IST Austria))

  • Edouard Hannezo

    (Institute of Science and Technology Austria (IST Austria))

  • Emmi Tiilikainen

    (Biomedicum Helsinki)

  • Inam Liaqat

    (Biomedicum Helsinki)

  • Emma Jakobsson

    (Biomedicum Helsinki)

  • Harri Nurmi

    (Biomedicum Helsinki
    Biomedicum Helsinki)

  • Kari Vaahtomeri

    (Biomedicum Helsinki
    Biomedicum Helsinki)

Abstract

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.

Suggested Citation

  • Mehmet Can Uçar & Edouard Hannezo & Emmi Tiilikainen & Inam Liaqat & Emma Jakobsson & Harri Nurmi & Kari Vaahtomeri, 2023. "Self-organized and directed branching results in optimal coverage in developing dermal lymphatic networks," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41456-7
    DOI: 10.1038/s41467-023-41456-7
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