Theory of branching morphogenesis by local interactions and global guidance

Mehmet Can Uçar (), Dmitrii Kamenev, Kazunori Sunadome, Dominik Fachet, Francois Lallemend, Igor Adameyko, Saida Hadjab () and Edouard Hannezo ()
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Mehmet Can Uçar: Institute of Science and Technology Austria
Dmitrii Kamenev: Karolinska Institutet
Kazunori Sunadome: Karolinska Institutet
Dominik Fachet: Institute of Science and Technology Austria
Francois Lallemend: Karolinska Institutet
Igor Adameyko: Karolinska Institutet
Saida Hadjab: Karolinska Institutet
Edouard Hannezo: Institute of Science and Technology Austria

Nature Communications, 2021, vol. 12, issue 1, 1-10

Abstract: Abstract 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27135-5

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DOI: 10.1038/s41467-021-27135-5

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