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Hierarchical patterning modes orchestrate hair follicle morphogenesis

Glover, James D.; Wells, Kirsty L.; Matthäus, Franziska; Painter, Kevin J.; Ho, William; Riddell, Jon; Johansson, Jeanette A.; Ford, Matthew J.; Jahoda, Colin A.B.; Klika, Vaclav; Mort, Richard L.; Headon, Denis J.

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James D. Glover

Kirsty L. Wells

Franziska Matthäus

Kevin J. Painter

William Ho

Jon Riddell

Jeanette A. Johansson

Matthew J. Ford

Vaclav Klika

Richard L. Mort

Denis J. Headon


Two theories address the origin of repeating patterns, such as hair follicles, limb digits, and intestinal villi, during development. The Turing reaction–diffusion system posits that interacting diffusible signals produced by static cells first define a prepattern that then induces cell rearrangements to produce an anatomical structure. The second theory, that of mesenchymal self-organisation, proposes that mobile cells can form periodic patterns of cell aggregates directly, without reference to any prepattern. Early hair follicle development is characterised by the rapid appearance of periodic arrangements of altered gene expression in the epidermis and prominent clustering of the adjacent dermal mesenchymal cells. We assess the contributions and interplay between reaction–diffusion and mesenchymal self-organisation processes in hair follicle patterning, identifying a network of fibroblast growth factor (FGF), wingless-related integration site (WNT), and bone morphogenetic protein (BMP) signalling interactions capable of spontaneously producing a periodic pattern. Using time-lapse imaging, we find that mesenchymal cell condensation at hair follicles is locally directed by an epidermal prepattern. However, imposing this prepattern’s condition of high FGF and low BMP activity across the entire skin reveals a latent dermal capacity to undergo spatially patterned self-organisation in the absence of epithelial direction. This mesenchymal self-organisation relies on restricted transforming growth factor (TGF) β signalling, which serves to drive chemotactic mesenchymal patterning when reaction–diffusion patterning is suppressed, but, in normal conditions, facilitates cell movement to locally prepatterned sources of FGF. This work illustrates a hierarchy of periodic patterning modes operating in organogenesis.


Glover, J. D., Wells, K. L., Matthäus, F., Painter, K. J., Ho, W., Riddell, J., …Headon, D. J. (2017). Hierarchical patterning modes orchestrate hair follicle morphogenesis. PLoS Biology, 15(7), Article e2002117.

Journal Article Type Article
Acceptance Date Jun 7, 2017
Online Publication Date Jul 11, 2017
Publication Date Jul 11, 2017
Deposit Date Aug 23, 2017
Publicly Available Date Aug 23, 2017
Journal PLoS Biology
Print ISSN 1544-9173
Electronic ISSN 1545-7885
Publisher Public Library of Science
Peer Reviewed Peer Reviewed
Volume 15
Issue 7
Article Number e2002117


Published Journal Article (25.2 Mb)

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Copyright Statement
© 2017 Glover et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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