A multi-scale model for hair follicles reveals heterogeneous domains driving rapid spatiotemporal hair growth patterning
- University of California, Irvine, United States
- School of Medicine, Kyungpook National University, Republic of Korea
- School of Medicine, Kyungpook National University, Korea (South), Republic of
- University of Queensland Diamantina Institute, Australia
- University of Southern California, United States
- Kyungpook National University Hospital, Republic of Korea
- Indiana University School of Medicine, United States
- College of Biological Sciences, China Agricultural University, China
Abstract
The control principles behind robust cyclic regeneration of hair follicles (HFs) remain unclear. Using multi-scale modeling we show that coupling inhibitors and activators with physical growth of HFs is sufficient to drive periodicity and excitability of hair regeneration. Model simulations and experimental data reveal that mouse skin behaves as a heterogeneous regenerative field, composed of anatomical domains where HFs have distinct cycling dynamics. Interactions between fast-cycling chin and ventral HFs and slow-cycling dorsal HFs produce bilaterally symmetric patterns. Ear skin behaves as a hyper-refractory domain with HFs in extended rest phase. Such hyper-refractivity relates to high levels of BMP ligands and WNT antagonists, in part expressed by ear-specific cartilage and muscle. Hair growth stops at the boundaries with hyper-refractory ears and anatomically discontinuous eyelids, generating wave-breaking effects. We posit that similar mechanisms for coupled regeneration with dominant activator, hyper-refractory, and wave-breaker regions can operate in other actively renewing organs.
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Funding
National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01-AR067273)
- Maksim V Plikus
National Research Foundation of Korea (2016R1C1B1015211)
- Ji Won Oh
National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01-AR061552)
- Krzysztof Kobielak
National Health and Medical Research Council (1023371)
- Kiarash Khosrotehrani
National Science Foundation (DGE-1321846)
- Christian Fernando Guerrero-Juarez
National Institute of General Medical Sciences (GM055246)
- Christian Fernando Guerrero-Juarez
Pew Charitable Trusts (29641)
- Maksim V Plikus
National Science Foundation (DMS 1161621)
- Qing Nie
National Cancer Institute (T32-CA009054)
- Hye-Lim Lee
National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01-AR056439)
- Bogi Andersen
National Science Foundation (DMS 1562176)
- Qing Nie
National Institute of General Medical Sciences (P50-GM076516)
- Qing Nie
National Institute of General Medical Sciences (R01-GM107264)
- Qing Nie
National Institute of Neurological Disorders and Stroke (R01-NS095355)
- Qing Nie
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#2012-3054 and #2013-3081) of the University of California, Irvine.
Copyright
© 2017, Wang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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