Interactions among the cells and matrices of the epidermis and mesenchyme of skin are essential for hair follicle initiation and development. The identification of receptors for epidermal growth factor (EGF) on epithelial components of the follicle during growth has suggested that the ligand participates in some of these events. We have used affinity-purified antibodies together with an alkaline phosphatase detection procedure to investigate the distribution of EGF in the skin of the sheep during wool follicle formation. Immunoreactivity was restricted to the periderm and intermediate layers of fetal epidermis at 55 d of gestation, when the first wave of wool follicles are initiated. This particular distribution persisted during subsequent development but never became associated with the basal cells of the epidermis. The activity was lost around 118 d, coinciding with sloughing of the periderm. No immunoreactivity was found in the plugs or the dermal condensations of the developing follicles. At approximately 105 d of gestation, however, reactions were detected in the outer root sheath as the follicles matured and in the differentiating cells of the sebaceous glands. A similar distribution pattern was also noted at 140 d, just prior to birth, and in adult animals, indicating that EGF was sequestered and perhaps synthesized within the follicle. The presence of immunoreactive material was also associated with the pilary canals and the skin surface, suggesting that this may have had its origin in the sebaceous glands. We examined this using a radioreceptor assay for EGF. Material washed from the skin surface and sebaceous gland extracts were found to displace 125I-EGF from rat liver membranes, in parallel with mouse EGF.
Wool follicles are classified into 3 major types: primary (P), original secondary (SO), and derived secondary (SD). They are formed during fetal life as successive waves of initiation pass through the skin. P follicles are the first to be initiated. SO follicles develop between the primaries and are separated from them at non-randomly distributed sites. SD follicles are the last to be initiated and branch from SO and other SD follicles. We have measured the densities of these follicles in 4 lines of sheep selected for different fleece characters. Primary follicle and total follicle densities (NP and NP + NS) were estimated by conventional procedures. The densities of pilary canals were also obtained to provide a measure of Np + NSO. Follicle counts in both adult and fetal animals showed that NP and NP + NSO were relatively constant across the lines. Predominantly, density differences were due to variations in the numbers of follicles initiated during the last wave, forming the derived secondary population. Changes in follicle densities were therefore effected by developmental mechanisms that increase or decrease the extent of branching rather than by altering the numbers of P and SO follicles. The results suggest firstly that the numbers of initiation sites for P or SO follicle formation in the fetus, corresponding to the pilary canals of adult skin, are limited. Secondly, the skin has the capacity to continue to initiate follicles after most or all of the sites have been occupied. It is concluded that the mechanisms controlling follicle initiation site densities and total follicle densities are independently regulated in the sheep. The observations are discussed in relation to factors that influence the densities of the different follicle types. The results have practical implications for changing fleece weight and fibre diameter through selective breeding.
Mutations of the X‐linked genes Tabby (Ta) in mice and EDA in humans result in developmental and functional abnormalities, primarily in the skin and hair follicles. Although both genes are believed to encode membrane‐associated proteins, it has been suggested that, in the mouse, the mutation is linked to a deficiency of epidermal growth factor (EGF). This study investigated relationships between the skin abnormalities of Ta mice and the EGF signal pathway. The distribution of endogenous EGF in tissues of Ta/Y and +/Y animals was examined and, because of its reported morphogenetic actions and ability to overcome receptor signalling defects in vivo, the effects of exogenous EGF on the hair follicle population were determined. EGF levels were similar in a number of tissues of Ta/Y and +/Y mice, but amounts in Ta/Y submaxillary glands were reduced, probably due to a smaller gland size. Exogenous EGF inhibited hair follicle development and decreased follicle density in both genotypes. It was concluded from comparisons of the distributions of EGF and its effects in skin with those in mice bearing mutations in the EGF signal pathway that the normal phenotype results from interactions between EGF and the Ta peptide in skin.
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