1. These results lend strong support to the idea that follicular stem cells are located in the bulge of the upper follicle. (Yang J-S, Lavker RM, Sun T-T. Upper human hair follicle contains a subpopulation of keratinocytes with superior in vitro proliferative potential. J Invest Dermatol 1993;101:652-659.)

Our View: In actuality, "the bulge" is bulges.

2. We have recently proposed that hair follicle stem cells reside in the bulge area of the upper follicle. We predicted that during early anagen the normally slow-cycling bulge stern cells may be activated by the abutting dermal papilla cells to undergo transient proliferation giving rise to keratinocytes of the lower follicle. (Wilson C, Cotsarelis G, Wei Z-G, Fryer E, Margolis-Fryer, Ostead M, Tokarek R, Sun T-T, Lavker RM. Cells within the bulge region of mouse hair follicle transiently proliferate during early anagen: heterogeneity and functional differences of various hair cycles. Differentiation 1994; 55:127-136.)

Our View: "The bulge" is unnecessary for initiation of a new follicular cycle because: (1) the follicular papilla in man resides at some distance from the bulge, (2) follicles in mammals other than man have no "bulge" and yet their follicles cycle, and (3) trichofolliculoma, a hamartoma, is devoid of muscles of hair erection and of bulges, but follicles in that condition cycle nonetheless.

3. Based on a number of observations, we now believe that the follicular epithelial germ cells are located in the bulge area. (Lavker RM, Miller S, Wilson C, Cotsarelis G, Wei Z-G, Yang J-S, Sun T-T. Hair follicle stem cells: their location, role in hair cycle; and involvement in skin tumor formation. J Invest Dermatol 1993;101(1) Suppl:16S-26S.)

Our View: Germinative cells are distributed along the entire periphery of a follicle and all of them are capable of giving rise to a follicle. So, too, are germinative cells at the periphery of the epithelium that lines an infundibular cyst, and, theoretically, are germinative cells of any epithelium. Germinative cells at the base of an isthmus in telogen, at the urgings of cells of a follicular papilla, seem to initiate the anagen phase of a cycle.

4. Follicular bulge cells may represent a population of pluripotent stem cells that can give rise to not only the hair follicle but also the epidermis and sebaceous glands. (Miller SJ, Wei Z-G, Wilson C, Dzubow L, Sun T-T, Lavker RM. Mouse skin is particularly susceptible to tumor initiation during early anagen ofthe hair cycle: possible involvement of hair follicle stem cells. J Invest Dermatol 1993; 101:591-594.)

Our View: "The bulge" is not responsible for re-population of epidermis; eccrine ductal and infundibular keratinocytes are. Mantles, not bulges, give rise to sebaceous units.

5. Even more important conceptually is the observation that a greater susceptibility in skin-tumor formation coincides with a time when the cells in the bulge region are transiently activated to proliferate. This strongly implies a role for these bulge cells in giving rise to some of the skin cancers [basal-cell carcinomas, keratoacanthomas], and is consonant with the hypothesis that these cells are stern cells. (Lavker RM, Miller S, Wilson C, Cotsarelis G, Wei 7_-G, Yang J-S, Sun T-T. Hair follicle stem cells: their location, role in hair cycle, and involvement in skin tumor formation. J Invest Dermatol 1993;101(1)Suppl:16S-26S.)

Our View: Cells of the bulge have never been shown to give rise to carcinomas.

6. Cells in the bulge of the mouse telogen follicle give rise to the lower anagen follicle. (Wilson C, Sun T-T, Lavker RM. Cells in the bulge of the mouse telogen follicle give rise to the lower anagen follicle. Skin Pharmacol 1994;7:8-11.)

Our View: There is no "bulge" in a follicle of a mouse. (See article by Dunstan and Linder in this issue.)