Active Wnt/β-catenin signaling in the dermal papilla (DP) is required for postnatal hair cycling. In addition, maintenance of the hair-inducing ability of DP cells in vitro requires external addition of Wnt molecules. However, whether DP cells are a critical source of Wnt ligands and induce both autocrine and paracrine signaling cascades to promote adult hair follicle growth and regeneration remains elusive. To address this question, we generated an animal model that allows inducible ablation of Wntless (Wls), a transmembrane Wnt exporter protein, in CD133-positive (CD133+) DP cells. CD133+ cells have been shown to be a specific subpopulation of cells in the DP, which possesses the hair-inducing capability. Here, we show that ablation of Wls expression in CD133+ DP cells results in a shortened period of postnatal hair growth. Mutant hair follicles were unable to enter full anagen (hair growth stage) and progressed toward a rapid regression. Notably, reduced size of the DP and decreased expression of anagen DP marker, versican, were observed in hair follicles when CD133+ DP cells lost Wls expression. Further analysis showed that Wls-deficient CD133+ DP cells led to reduced proliferation and differentiation in matrix keratinocytes and melanocytes that are needed for the generation of the hair follicle structure and a pigmented hair shaft. These findings clearly demonstrate that Wnt ligands produced by CD133+ DP cells play an important role in postnatal hair growth by maintaining the inductivity of DP cells and mediating the signaling cross-talk between the mesenchyme and the epithelial compartment.
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October 2016
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Crystal structure of human hemoglobin β subunit (PDB ID: 1A3N) with an in silico mutation of phenylalanine 41 to tyrosine (green) to enhance function as a blood substitute; image kindly provide by Brandon Reeder and Chris Cooper (University of Essex). For details see Silkstone et al. in this issue (pages 3371–3383).
Research Article|
September 27 2016
CD133-positive dermal papilla-derived Wnt ligands regulate postnatal hair growth
Linli Zhou;
Linli Zhou
1Division of Pharmaceutical Sciences, College of Pharmacy, University of Cincinnati, Cincinnati, OH 45267, USA
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Kun Yang;
Kun Yang
1Division of Pharmaceutical Sciences, College of Pharmacy, University of Cincinnati, Cincinnati, OH 45267, USA
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April Carpenter;
April Carpenter
2Division of Pediatric Ophthalmology and Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA
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Richard A. Lang;
Richard A. Lang
2Division of Pediatric Ophthalmology and Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA
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Thomas Andl;
Thomas Andl
3Burnett School of Biological Sciences, University of Central Florida, Orlando, FL 32816, USA
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Yuhang Zhang
Yuhang Zhang
1Division of Pharmaceutical Sciences, College of Pharmacy, University of Cincinnati, Cincinnati, OH 45267, USA
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Publisher: Portland Press Ltd
Received:
May 19 2016
Revision Received:
July 21 2016
Accepted:
July 26 2016
Accepted Manuscript online:
July 26 2016
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society
2016
Biochem J (2016) 473 (19): 3291–3305.
Article history
Received:
May 19 2016
Revision Received:
July 21 2016
Accepted:
July 26 2016
Accepted Manuscript online:
July 26 2016
Citation
Linli Zhou, Kun Yang, April Carpenter, Richard A. Lang, Thomas Andl, Yuhang Zhang; CD133-positive dermal papilla-derived Wnt ligands regulate postnatal hair growth. Biochem J 1 October 2016; 473 (19): 3291–3305. doi: https://doi.org/10.1042/BCJ20160466
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