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Molecular and Cellular Biology, March 2005, p. 1696-1712, Vol. 25, No. 5
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.5.1696-1712.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Epithelium-Mesenchyme Interactions Control the Activity of Peroxisome Proliferator-Activated Receptor ß/{delta} during Hair Follicle Development

Nicolas Di-Poï,1 Chuan Young Ng,1 Nguan Soon Tan,1 Zhongzhou Yang,2 Brian A. Hemmings,2 Béatrice Desvergne,1 Liliane Michalik,1 and Walter Wahli1*

Center for Integrative Genomics, NCCR Frontiers in Genetics, University of Lausanne, Lausanne,1 Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland2

Received 26 July 2004/ Returned for modification 26 August 2004/ Accepted 18 November 2004

Hair follicle morphogenesis depends on a delicate balance between cell proliferation and apoptosis, which involves epithelium-mesenchyme interactions. We show that peroxisome proliferator-activated receptor beta/delta (PPARß/{delta}) and Akt1 are highly expressed in follicular keratinocytes throughout hair follicle development. Interestingly, PPARß/{delta}- and Akt1-deficient mice exhibit similar retardation of postnatal hair follicle morphogenesis, particularly at the hair peg stage, revealing a new important function for both factors in the growth of early hair follicles. We demonstrate that a time-regulated activation of the PPARß/{delta} protein in follicular keratinocytes involves the up-regulation of the cyclooxygenase 2 enzyme by a mesenchymal paracrine factor, the hepatocyte growth factor. Subsequent PPARß/{delta}-mediated temporal activation of the antiapoptotic Akt1 pathway in vivo protects keratinocytes from hair pegs against apoptosis, which is required for normal hair follicle development. Together, these results demonstrate that epithelium-mesenchyme interactions in the skin regulate the activity of PPARß/{delta} during hair follicle development via the control of ligand production and provide important new insights into the molecular biology of hair growth.

* Corresponding author. Mailing address: Center for Integrative Genomics, Biology Building, University of Lausanne, CH-1015 Lausanne, Switzerland. Phone: 41 21 692 4111. Fax: 41 21 692 4115. E-mail: walter.wahli{at}unil.ch.

Molecular and Cellular Biology, March 2005, p. 1696-1712, Vol. 25, No. 5
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.5.1696-1712.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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