Hair Cycle Resting Phase Is Regulated by Cyclic Epithelial FGF18 Signaling

Journal of Investigative Dermatology (2012) 132, 1338–1345; doi:10.1038/jid.2011.490; published online 2 February 2012
Miho Kimura-Ueki1,2, Yuko Oda1,2, Junko Oki1, Akiko Komi-Kuramochi1, Emi Honda1, Masahiro Asada1, Masashi Suzuki1 and Toru Imamura1

1Signaling Molecules Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan
2These authors contributed equally to this work.

Received 22 July 2011; Revised 25 November 2011; Accepted 11 December 2011
Advance online publication 2 February 2012

Abstract

Hair follicles repeatedly cycle through growth (anagen), regression (catagen), and resting (telogen) phases. Although the signaling molecules involved in the anagen and anagen–catagen transition have been studied extensively, the signaling that controls telogen is only partly understood. Here we show that fibroblast growth factor (Fgf)18 is expressed in a hair stem cell niche throughout telogen, and that it regulates the hair cycle through the non-growth phases. When the Fgf18 gene is conditionally knocked out in keratin 5-positive epithelial cells in mice, telogen becomes very short, giving rise to a strikingly rapid succession of hair cycles. In wild-type mice, hair follicle growth during anagen is strongly suppressed by local delivery of FGF18 protein. Our results demonstrate that epithelial FGF18 signaling and its reduction in the milieu of hair stem cells are crucial for the maintenance of resting and growth phase, respectively.