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Inflationary theory of branching morphogenesis in the mouse salivary gland.

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Bordeu, Ignacio 
Chatzeli, Lemonia 


The mechanisms that regulate the patterning of branched epithelia remain a subject of long-standing debate. Recently, it has been proposed that the statistical organization of multiple ductal tissues can be explained through a local self-organizing principle based on the branching-annihilating random walk (BARW) in which proliferating tips drive a process of ductal elongation and stochastic bifurcation that terminates when tips encounter maturing ducts. Here, applied to mouse salivary gland, we show the BARW model struggles to explain the large-scale organization of tissue. Instead, we propose that the gland develops as a tip-driven branching-delayed random walk (BDRW). In this framework, a generalization of the BARW, tips inhibited through steric interaction with proximate ducts may continue their branching program as constraints become alleviated through the persistent expansion of the surrounding tissue. This inflationary BDRW model presents a general paradigm for branching morphogenesis when the ductal epithelium grows cooperatively with the domain into which it expands.


Acknowledgements: We are grateful for illuminating discussions with Edouard Hannezo and members of the Simons lab, especially Yanbo Yin for his help with the live-imaging. This study was supported by grants to B.D.S. (EPSRC, EP/P034616/1, Wellcome Trust, 098357/Z/12/Z and 219478/Z/19/Z, and Royal Society EP Abraham Research Professorship, RP/R1/180165), L.C. (Herchel Smith Postdoctoral Fellowship Fund) and I.B. (FONDECYT, 11230941, VID, UI-015/22). The research team also acknowledges core support from the Wellcome Trust (092096) and CRUK (C6946/A14492). We also acknowledge staff at the Gurdon Institute Imaging Facility for microscopy and image analysis support. For the purpose of open access, the authors have applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising from this submission.

Funder: Royal Society EP Abraham Research Professorship, RP/R1/180165.

Funder: VID (Universidad de Chile) Grant No UI-015/22

Funder: Herchel Smith Postdoctoral Fellowship Fund


Mice, Animals, Epithelium, Morphogenesis, Salivary Glands

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Nat Commun

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Springer Science and Business Media LLC
Wellcome Trust (098357/Z/12/Z)
Wellcome Trust (219478/Z/19/Z)
Engineering and Physical Sciences Research Council (NS/A000045/1)
Royal Society (RP/R1/180165)
Cancer Research UK (23363)
Engineering and Physical Sciences Research Council (EP/P034616/1)
Wellcome Trust (092096/Z/10/Z)
Cancer Research Uk (None)
Wellcome Trust Royal Society EPSRC