Editors' ChoiceHair

Cycling in Synchrony

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Science Signaling  22 Jan 2008:
Vol. 1, Issue 3, pp. ec25
DOI: 10.1126/stke.13ec25

Hair follicles cycle through growth, involution, and resting phases, with entry into the anagen (or growth) phase depending on activation of hair stem cells. Following anagen, there is a refractory period that has been postulated to depend on an inhibitory substance called "chalone." Whereas cycling in individual follicles depends on periodic activation of the Wnt effector β-catenin, hair regeneration in various mammalian species occurs in coordinated waves, and the mechanism whereby cycling in populations of follicles is coordinated has been unclear. Plikus et al. analyzed cycling of hair follicle domains (in which cycling is coordinated) and found that there was a minimum 28-day telogen (resting) phase, which they defined as "early telogen," followed by a "late telogen" phase of 0 to 60 days. Entry into anagen after hair plucking was faster for hairs in late telogen than for hairs in early telogen, indicating that early telogen correlated with the refractory period. Experiments with lacZ reporter mice revealed that interfollicular expression of bone morphogenetic protein 2 (Bmp2) and Bmp4 fluctuated with hair cycles, such that BMP signaling was out of phase with Wnt signaling. Bmp expression, which was not apparent in early anagen, rose during anagen and remained active during early (refractory) telogen but disappeared in late telogen. Similarly, Smad 1/5/8 is active (phosphorylated) in refractory follicles but not during late telogen. Overexpression of the BMP antagonist noggin shortened the refractory phase, whereas administration of BMP4 ahead of an anagen wave caused local follicles to become refractory, and experiments involving skin grafts from Nog-overexpressing to wild-type mice revealed mutual effects of host and donor on follicle cycling. Thus the authors conclude that BMP signaling regulates and coordinates regional hair follicle cycling and may constitute the long-postulated inhibitory "chalone."

M. V. Plikus, J. A. Mayer, D. de la Cruz, R. E. Baker, P. K. Maini, R. Maxson, C.-M. Chuong, Cyclic dermal BMP signalling regulates stem cell activation during hair regeneration. Nature 451, 340-344 (2008). [PubMed]

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