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A Unifying Theory of Branching Morphogenesis

Lookup NU author(s): Dr Mohammad Moad, Dr Rakesh Heer

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2017 The Author(s) The morphogenesis of branched organs remains a subject of abiding interest. Although much is known about the underlying signaling pathways, it remains unclear how macroscopic features of branched organs, including their size, network topology, and spatial patterning, are encoded. Here, we show that, in mouse mammary gland, kidney, and human prostate, these features can be explained quantitatively within a single unifying framework of branching and annihilating random walks. Based on quantitative analyses of large-scale organ reconstructions and proliferation kinetics measurements, we propose that morphogenesis follows from the proliferative activity of equipotent tips that stochastically branch and randomly explore their environment but compete neutrally for space, becoming proliferatively inactive when in proximity with neighboring ducts. These results show that complex branched epithelial structures develop as a self-organized process, reliant upon a strikingly simple but generic rule, without recourse to a rigid and deterministic sequence of genetically programmed events.


Publication metadata

Author(s): Hannezo E, Scheele CLGJ, Moad M, Drogo N, Heer R, Sampogna RV, van Rheenen J, Simons BD

Publication type: Article

Publication status: Published

Journal: Cell

Year: 2017

Volume: 171

Issue: 1

Pages: 242-255.e27

Print publication date: 21/09/2017

Online publication date: 21/09/2017

Acceptance date: 15/08/2017

ISSN (print): 0092-8674

ISSN (electronic): 1097-4172

Publisher: Cell Press

URL: https://doi.org/10.1016/j.cell.2017.08.026

DOI: 10.1016/j.cell.2017.08.026


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