L6.      Involvement of EDAR signalling in the control of hair follicle involution (catagen).
Michael Fessing, Tatyana Sharova, Andrey Sharov, Ruzanna Atoyan, Vladimir Botchkarev; Department of Dermatology, Boston University School of Medicine, USA.

Ectodysplasin (Eda) and its receptor (Edar) are required for normal development of several ectodermal derivatives including hair follicles (HFs). Here, we show that during murine hair cycle the expression of EdaA1, Edar, EDARADD and TRAF6 transcripts are minimal in the resting phase and maximal during HF transition from active growth to the regression (catagen). EdaA1 mRNA and Edar proteins are expressed in the hair matrix, outer and inner root sheaths of anagen HFs. During catagen, EdaA1 mRNA and Edar protein are expressed in the outer and inner root sheaths and later in the secondary hair germ. Catagen development accompanied by significantly increased number of TUNEL-positive cells in the outer root sheath is significantly accelerated in downless mice or after treatment of wild-type mice by fusion protein that inhibits Edar signaling, compared to the corresponding controls. Microarray, real-time PCR and immunohistochemical analyses of skin of downless mice reveal strong decrease of expression of X-linked inhibitor of apoptosis protein (XIAP), compared to the controls, suggesting XIAP as a target for Edar signaling. Thus, our data demonstrate that in addition to its well-established role in HF morphogenesis, Edar signaling is also involved in hair cycle control at least in part by regulating apoptosis in HF keratinocytes during catagen.