Bruce K. Wetzel

Barrier requirements as the evolutionary “driver” of epidermal pigmentation in humans

Current explanations for the development of epidermal pigmentation during human evolution are not tenable as stand‐alone hypotheses. Accordingly, we assessed instead whether xeric‐ and UV‐B‐induced stress to the epidermal permeability barrier, critical to survival in a terrestrial environment, could have “driven” the development of epidermal pigmentation. (1) Megadroughts prevailed in central Africa when hominids expanded into open savannahs [≈1.5–0.8 million years ago], resulting in sustained exposure to both extreme aridity and erythemogenic UV‐B, correlating with genetic evidence that pigment developed ≈1.2 million years ago. (2) Pigmented skin is endowed with enhanced permeability barrier function, stratum corneum integrity/cohesion, and a reduced susceptibility to infections. The enhanced function of pigmented skin can be attributed to the lower pH of the outer epidermis, likely due to the persistence of (more‐acidic) melanosomes into the outer epidermis, as well as the conservation of genes associated with eumelanin synthesis and melanosome acidification (e.g., TYR, OCA2 [p protein], SLC24A5, SLC45A2, MATP) in pigmented populations. Five keratinocyte‐derived signals (stem cell factor⇒KIT; FOXn1⇒FGF2; IL‐1α, NGF, and p53) are potential candidates to have stimulated the sequential development of epidermal pigmentation in response to stress to the barrier. We summarize evidence here that epidermal interfollicular pigmentation in early hominids likely evolved in response to stress to the permeability barrier. Am. J. Hum. Biol., 2010.

Evidence that stress to the epidermal barrier influenced the development of pigmentation in humans

It is widely assumed that the epidermis of early hominids lacked pigmentation, as does the skin of their primate ancestors (Jablonski and Chaplin, 2000; Westerhof, 2007). Several theories have been advanced to explain the subsequent latitude-dependent development and divergence of human pigmentation, including still widely held hypotheses that pigmentation evolved to protect against either genotoxic mutations that favor development of skin cancer (Goding, 2007; Robins, 1991), or against UV-induced nutrient photolysis (Jablonski, 1999; Jablonski and Chaplin, 2000). Although tyrosinase-positive, melanin-producing cells are widely distributed in exposed surfaces from fungi to primates (Epel et al., 1999), melanocytes are also present in some extracutaneous tissues with no exposure to the external environment. This wide distribution, plurifunctionality, and conservation throughout vertebrate evolution implies roles for melanin that extend beyond a need for defense against genotoxic or photolytic doses of ultraviolet light (UV) exposure (Blois, 1968; Deol, 1975; Mackintosh, 2001).

Osmium tetroxide-zinc iodide staining of Golgi elements and surface coats of hydras.

Hydras treated for 4 hours with osmium tetroxide-zinc iodide (OZI) exhibit complete impregnation of Golgi saccules and vesicles, staining of the fibrillar surface coat of the gastrodermis, and staining of the inner surface of certain clear, intracellular vacuoles. No deposition occurs within the epidermal surface coat, the intercellular spaces, or the mesoglea. When the OZI solution is adjusted to pH 7.0, Golgi structures stain, but deposition along surface coats is no longer noted. Increased or decreased duration of treatment with OZI produces incomplete Golgi permeation and variable loss of surface coat staining. Hyaluronidase pretreatment of living hydras prevents OZI deposition along the gastrodermal luminal surface and within Golgi zones, suggesting that OZI could be staining mucosaccharides in these sites.

Rapid membrane changes in mouse epithelial cells after exposure to epidermal growth factor

Cells of the recently established epithelial mouse embryo cell line, MMC-E, possess abundant surface receptors for the polypeptide hormone, epidermal growth factor (EGF). The influence of EGF on these cells and on the human epidermoid carcinoma line, A431, was compared by scanning electron microscopy (SEM) and light microscopy. Within seconds after the addition of medium containing 100 ng/ml EGF, the MMC-E cells uniformly develop marginal surface ruffles in association with macropinocytosis, and these activities subside within 1 hr. The addition of fresh prewarmed medium lacking EGF elicits no discernible change in MMC-E cell morphology over this period. In contrast, cells of the human epidermoid carcinoma line, A431, respond less uniformly and the addition of fresh prewarmed medium lacking EGF elicits similar changes in these cells. Thus, the stable nontransformed MMC-E mouse epithelial cell line may prove an especially promising model for studies of the action of polypeptide growth factors on epithelial cell biology.

Epidermal growth factor-induced alterations in proliferating mouse epithelial cells

Abstract The effects of epidermal growth factor (EGF) on the growth and morphology of mouse embryo epithelial cells (MMC-E) were studied in culture. Growing cultures of epithelial cells were incubated in the media containing EGF or certain other mitogenic peptides. It was found that nanogram (ng) quantities of EGF stimulated growth in these cells and caused reversible phenotypic changes in these cells. These changes were not observed in cultures treated with the other mitogens. The compact growing islands of MMC-E cells were surrounded by elongated border cells [12]. EGF induced the elongated border cells to flatten and spread. The change of the elongated border cells into polygonal, flattened cells was dependent on the dose of EGF. After treatment with higher concentrations of EGF all cells appeared more flattened and their cytoplasm was more granular than that of the controls. Scanning electron microscopic studies (SEM) showed that the elongated border cells in the control cultures were distinctly higher than the cells inside the islands, while after exposure to EGF they flattened and had fewer surface microvilli than control cells. When EGF was removed and the cells were further cultivated in media without EGF, the border cells became smaller and elongated, eventually resembling those in the control cultures. These results show that EGF may act as a regulatory factor in the control of the proliferation and differentiation of mouse epithelial cells.