Control of hair follicle cell fate by underlying mesenchyme through a CSL–Wnt5a–FoxN1 regulatory axis
- Bing Hu1,
- Karine Lefort1,
- Wenying Qiu1,
- Bach-Cuc Nguyen2,
- Renuga Devi Rajaram3,
- Einar Castillo1,
- Fenglei He4,
- Yiping Chen4,
- Peter Angel5,
- Cathrin Brisken3 and
- G. Paolo Dotto1,2,6
- 1Department of Biochemistry, University of Lausanne, Epalinges CH-1066, Switzerland;
- 2Cutaneous Biology Research Center, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA;
- 3Swiss Institute for Experimental Cancer Research, Ecole Polytechnique Fédérale de Lausanne, Epalinges CH-1066, Switzerland;
- 4Department of Cell and Molecular Biology, Tulane University, New Orleans, Louisiana 70118, USA;
- 5German Cancer Research Center, Heidelberg D-69120, Germany
Abstract
Epithelial–mesenchymal interactions are key to skin morphogenesis and homeostasis. We report that maintenance of the hair follicle keratinocyte cell fate is defective in mice with mesenchymal deletion of the CSL/RBP-Jκ gene, the effector of “canonical” Notch signaling. Hair follicle reconstitution assays demonstrate that this can be attributed to an intrinsic defect of dermal papilla cells. Similar consequences on hair follicle differentiation result from deletion of Wnt5a, a specific dermal papilla signature gene that we found to be under direct Notch/CSL control in these cells. Functional rescue experiments establish Wnt5a as an essential downstream mediator of Notch–CSL signaling, impinging on expression in the keratinocyte compartment of FoxN1, a gene with a key hair follicle regulatory function. Thus, Notch/CSL signaling plays a unique function in control of hair follicle differentiation by the underlying mesenchyme, with Wnt5a signaling and FoxN1 as mediators.
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Footnotes
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↵6 Corresponding author.
E-MAIL paolo.dotto{at}unil.ch; FAX 41-21-692-5705.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1886910.
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Supplemental material is available at http://www.genesdev.org.
- Received November 18, 2009.
- Accepted June 8, 2010.
- Copyright © 2010 by Cold Spring Harbor Laboratory Press