A multi-scale model for hair follicles reveals heterogeneous domains driving rapid spatiotemporal hair growth patterning

Qixuan Wang, Ji Won Oh, Hye Lim Lee, Anukriti Dhar, Tao Peng, Raul Ramos, Christian Fernando Guerrero-Juarez, Xiaojie Wang, Ran Zhao, Xiaoling Cao, Jonathan Le, Melisa A. Fuentes, Shelby C. Jocoy, Antoni R. Rossi, Brian Vu, Kim Pham, Xiaoyang Wang, Nanda Maya Mali, Jung Min Park, June Hyug ChoiHyunsu Lee, Julien M.D. Legrand, Eve Kandyba, Jung Chul Kim, Moonkyu Kim, John Foley, Zhengquan Yu, Krzysztof Kobielak, Bogi Andersen, Kiarash Khosrotehrani, Qing Nie, Maksim V. Plikus

Research output: Contribution to journalArticle

18 Scopus citations

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.

Original languageEnglish (US)
Article numbere22772
JournaleLife
Volume6
DOIs
StatePublished - Jul 11 2017

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ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Wang, Q., Oh, J. W., Lee, H. L., Dhar, A., Peng, T., Ramos, R., Guerrero-Juarez, C. F., Wang, X., Zhao, R., Cao, X., Le, J., Fuentes, M. A., Jocoy, S. C., Rossi, A. R., Vu, B., Pham, K., Wang, X., Mali, N. M., Park, J. M., ... Plikus, M. V. (2017). A multi-scale model for hair follicles reveals heterogeneous domains driving rapid spatiotemporal hair growth patterning. eLife, 6, [e22772]. https://doi.org/10.7554/eLife.22772