Margaret H. Hardy

The secret life of the hair follicle.

The mammalian hair follicle is a treasure waiting to be discovered by more molecular geneticists. How can a tiny cluster of apparently uniform epithelial cells, adjacent to a tiny cluster of uniform mesenchymal cells, give rise to five or six concentric cylinders, each of which is composed of cells of a distinctive type that synthesize their own distinctive set of proteins? There is now evidence that several growth factors, cell adhesion molecules and other molecules play important roles in the regulation of this minute organ.

The effects of vitamin A on the epidermis of the fetal mouse in organ culture--an ultrastructural study.

Skin pieces from 14-day fetal mice were cultivated for 1, 2, 3, 6, 7, and 10 days, then fixed in Zenkers fluid or glutaraldehyde for study by light and transmission electron microscopy. Epidermal differentiation in the standard culture medium was similar to that observed in vivo. When 6 μg/ml of retinol was added to the medium, discontinuities appeared in the basal lamina after 1 day. These gaps persisted after 2, 3, and 6 days, permitting numerous close contacts between basal epidermal cells and dermal cell processes. After 3 days in vitamin A medium, new “periderm-like” granules appeared in the stratum granulosum. Tonofilament bundles were less numerous than in normal medium, whereas Golgi stacks and vesicles were more numerous. It is suggested that basal lamina breakdown may permit the redirection of epidermal cell differentiation in the presence of vitamin A.

The expression of the gene asebia in the laboratory mouse: 2. Hair follicles

Mice homozygous for the asebia mutation ( ab / ab ) are char1acterized by defective sebaceous glands, a short sparse hair coat from 7 days and progressive alopecia. In addition, we have found that the initial hair follicle rudiments in the skin of these mice are able to differentiate into relatively normal anagen follicles which are often excessive in length and have minor abnormalities of the inner and outer root sheath components. The inner root sheath fails to form the typical transverse corrugations at the level of the sebaceous glands and its cells apparently remain, partially undegraded, plugging the hair canal and adhering to emerging hair shafts. Defects noted in the outer root sheath may be responsible for the failure of inner root sheath degradation. With increasing age, irregularities in hair cycle duration, loss of the originally parallel arrangement of hair follicles and further abnormalities of the individual follicular components are increasingly evident. Follicles in asebic mice have a tendency to form buds and branches which occasionally begin typical follicular differentiation. The consistent failure of the asebic follicles to pass normally through the catagen stage to the telogen stage results in long twisted follicles with abnormal and often loosely anchored hair clubs. The dermal papillae are often abnormal or absent from telogen follicles, while typical germ cells are not formed. Thus the lack of multiple hair follicles, the disorganization of follicles and the progressive alopecia observed in the asebic mice are accounted for. It is suggested that the altered dermal environment and outer root sheath abnormalities may be responsible for many of the follicular defects.

The use of retinoids as probes for analyzing morphogenesis of glands from epithelial tissues

SummaryThirty-five years ago Honor Fell and Edward Mellanby were studying effects of high doses of vitamin A on skeletal development in chick embryos when they noticed that a piece of epidermis, accidentally included in an organ culture, had undergone mucous metaplasia. Further studies by Fell and others eventually led to an understanding of the important role of vitamin A in modulating epithelia in vivo. Fifteen years later another organ culture experiment showed me that excess vitamin A could also initiate the morphogenesis of branching and mucus-secreting glands from developing vibrissa follicles in upper lip skin of embryonic mice. Since then our group has shown that induction of this novel structure by naturally occurring retinoids resembles a normal embryonic induction in that it is stage-dependent, time-dependent, and irreversible. Tissue separation and recombination studies showed that isolated upper lip epidermis can form these glands when combined with retinoid-treated upper lip dermis. Untreated mouse epidermis can form similar glands after combination with chick dermis containing higher retinoid levels. The hamster cheek pouch, normally devoid of glandular structures, can also form mucous glands when treated with a retinoid, either in vivo or in vitro. Recombination studies in organ culture have now shown that mesenchyme exposed to retinoid is essential for gland morphogenesis from pouch epithelium. Evidences is accumulating that retinoic acid may even be the active morphogen in some normally developing systems.

Localization of vitamin a by autofluorescence during induced metaplastic changes in cultures of skin

SummaryA technique was devised for following the uptake and location of vitamin A in organ cultures. Explants of 12- and 13-day embryonic mouse upper lip skin were grown for 3,6 or 9 days in biological medium to which was added 0,4.1 or 6.9 μg per ml of retinyl acetate. This form of vitamin A caused glandular morphogenesis of vibrissa follicles, and keratinization in epidermis and follicles was completely suppressed in 12-day explants and partially suppressed in 13-day explants. Frozen sections at 16 μm showed the white, non-fading fluorescence of keratin and the green, rapidly-fading fluorescence due to vitamin A which was captured by high-speed photography. Although more concentrated within lipid droplets in the dermis, the vitamin penetrated both the epidermis and the hair follicles. The ability to obtain permanent photographic records of the fading fluorescence makes this a useful method for analyzing vitamin A distribution as well as keratin distribution.