Figure 2. Periodic Bmp signaling in the dermis and subcutaneous adipose tissue.

(a) Different temporal stages are spatially laid across the skin strip. The dark field illumination shows hair follicles (white) and Bmp2 in situ hybridization (green). Note the two are out of phase.

An, anagen; Comp, competent; Refr, refractory; Tel, telogen. Open arrows, the direction of the spreading waves; --| sign, boundary between anagen and refractory telogen.

(b, b′) Enlarged regions from boxed region of a. It shows details of Bmp2 expression during anagen spreading (b) and on the border of anagen VI – refractory telogen (b′). (b″), While later refractory telogen region becomes competent, anagen VI follicles still do not propagate.

(c) A long skin strip includes two segments of dermal Bmp on and off expression.

(d, e) Bmp2 and Bmp4 expressions are detected by semi-quantitative RT-PCR and in situ.

(f) pSMAD immuno-staining is present in follicular epithelium, including bulge area (insert) and adjoining infundibulum (green arrow). (f′) Since skin in its second telogen phase (45–70 day after birth) is usually used in hair follicle and carcinogenesis studies, we show results at this stage, which are consistent with older mice.

(g) Bmp2 expression (blue) co-localized within some Sudan red-positive adipocytes (red).

(h) Schematic summary of the hair cycle rhythm (black) and newly identified dermal rhythm (red). Together, they define 4 new functional stages. Catagen is omitted for simplification. Scale bars: a: 1 mm; b: 500 um; e–g: 200 um.