Mammalian skin evolution: a reevaluation.

A 1972 model for the evolutionary origin of hair suggested a primary mechanoreceptor role improving behavioral thermoregulation contributed to the success of late Paleozoic mammal-like reptiles. An insulatory role appeared secondarily subsequent to protohair multiplication. That model is updated in light of new data on (a) palaeoecology of mammalian ancestors; (b) involvement of HRPs in keratinization; (c) lipogenic lamellar bodies that form the barrier to cutaneous water loss; and (d) growth factors involved in hair follicle embryogenesis and turnover. It is now proposed that multiplication of sensory protohairs caused by mutations in patterning genes initially protected the delicate barrier tissues and eventually produced the minimal morphology necessary for an insulatory pelage. The latter permitted Mesozoic mammals to occupy the nocturnal niche 'in the shadow of dinosaurs'. When the giant reptiles became extinct, mammals underwent rapid radiation and reemerged as the dominant terrestrial vertebrates.

Nonavian feathers in a late Triassic archosaur.

Longisquama insignis was an unusual archosaur from the Late Triassic of central Asia. Along its dorsal axis Longisquama bore a series of paired integumentary appendages that resembled avian feathers in many details, especially in the anatomy of the basal region. The latter is sufficiently similar to the calamus of modern feathers that each probably represents the culmination of virtually identical morphogenetic processes. The exact relationship of Longisquama to birds is uncertain. Nevertheless, we interpret Longisquama's elongate integumentary appendages as nonavian feathers and suggest that they are probably homologous with avian feathers. If so, they antedate the feathers of Archaeopteryx, the first known bird from the Late Jurassic.

Ultrastructural contributions to an understanding of the cellular mechanisms involved in lizard skin shedding with comments on the function and evolution of a unique Lepidosaurian phenomenon.

Previous reports on the fine structure of lizard epidermis are confirmed and extended by SEM and TEM observations of cell differentiation and the form of shed material from the American anole Anolis carolinensis. Attention is drawn to two issues: 1) the tips of the spinules arising from the mature oberhautchen are markedly curved; this morphology can be seen during differentiation; 2) the median keels of scales from all parts of the body show "naked" oberhautchen cells that lack characteristic spinules, but have a membrane morphology comprising a complex system of serpentine microridges. Maderson's ([1966] J. Morphol. 119:39-50) "zip-fastener" model for the role of the shedding complex formed by the clear layer and oberhautchen is reviewed and extended in the light of recent SEM data. Apparently periodic lepidosaurian sloughing permits somatic growth; understanding how the phenomenon is brought about requires integration of data from the organismic to the molecular level. The diverse forms of integumentary microornamentation (MO) reported in the literature can be understood by considering how the cellular events occurring during the renewal phase prior to shedding relate to the emergence of the form-function complex of the ß-layer, which provides physical protection. Issues concerning the evolutionary origin of lepidosaurian skin-shedding are discussed. J. Morphol. 236:1-24, 1998. © 1998 Wiley-Liss, Inc.

Ultrastructural organization of avian stratum corneum lipids as the basis for facultative cutaneous waterproofing.

The ultrastructure of naked neck epidermis from the ostrich (Struthio camelus) and ventral apterium from watered, and water-deprived, Zebra finches (Taeniopygia [Poephila] guttata castanotis) is presented. The form and distribution of the fully differentiated products of the lipid-enriched multigranular bodies are compared in biopsies post-fixed with osmium tetroxide or ruthenium tetroxide. The fine structure of ostrich epidermis suggests it is a relatively poor barrier to cutaneous water loss (CWL). The fine structure from watered, and 16-hr water-deprived Zebra finches, considered in conjunction with measurements of CWL, confirms previous reports of "facultative waterproofing," and emphasizes the rapidity of tissue response to dehydration. The seemingly counterintuitive facts that one xerophilic avian species, the ostrich, lacks a "good barrier" to CWL, whereas another, the Zebra finch, is capable of forming a good barrier, but does not always express this capability, are discussed. An explanation of these data in comparison to mammals centers on the dual roles of the integument of homeotherms in thermoregulation and conserving body water. It is concluded that birds, whose homeothermic control depends so much on CWL, cannot possess a permanent "good barrier," as such would compromise the heat loss mechanism. Facultative waterproofing (also documented in lizards) protects the organism against sudden reductions in water availability. In birds, and probably in snakes and lizards, facultative waterproofing involves qualitative changes in epidermal cell differentiation. Possible control mechanisms are discussed.

Acetaminophen toxicity is substantially reduced by beta-carotene in mice.

Acetaminophen is toxic in overdose and even at routine therapeutic doses in glutathione-deficient populations such as alcoholics and AIDS patients. We were intrigued by the fact that beta-carotene is stored in the liver, the major organ of detoxification, and we speculated that dietary supplementation of beta-carotene would enhance the liver's ability to withstand toxic challenge from acetaminophen. We present a series of experiments which demonstrate that beta-carotene can prevent death or ameliorate toxicity from acetaminophen in mice.

Interaction between thermal environments and hormones affecting skin-shedding frequency in the tokay (Gekko gecko) (Gekkonidae, Lacertilia).

Effects of thyroidectomy and/or hypophysectomy on the skin-shedding frequency (SF) in the tokay Gekko gecko and of thyroid hormones on the oxygen consumption (OCR) at various temperature regimes have been determined. Surgery invariably protracted the cycle length, thus decreasing SF; the extent of these changes was temperature dependent, the higher the temperature, the less the difference. Effects of hypophysectomy on cycle length were expressed in two phases; an extended first post-operative cycle was followed by a further extended second post-operative cycle, with cycle length forming a plateau thereafter. With time, the operated tokays would die without shedding during a greatly protracted cycle. OCRs in the tokay were temperature dependent, but between 28 and 34 degrees C, no significant difference could be seen. Effects of thyroid hormones on OCR were also temperature dependent. Furthermore, tokays having higher OCR were shown to have shorter cycles and vice versa. Results showed that whatever effect hormone(s) have on SF is indirect through general metabolic changes. SF is merely a reflection of the general metabolic status of the animal. It is proposed that the role of hormone(s), those of the thyroid in particular, is to act as "fine-tuning" devices in the regulation of metabolism and, as such, of the viability of the animal.

Ultrastructural observations on the embryonic development of the integument of Lacerta muralis (Lacertilia, Reptilia).

Integumentary development on the dorsal and ventral aspects of the body of 14, 21, 26, 33, and 40-day incubated embryos of the European Wall Lizard (Lacerta muralis) is described. While the earliest stages of epidermal differentiation resemble those reported for other tetrapods, precocious differentiation of dermal collagen more resembles that of anamniotes than that of birds and mammals. Anchoring complexes comprising cellular components, anchor filaments, and collagen are described, and their possible relationship to the formation of scale anlagen is discussed. The first embryonic epidermal generation differentiates beneath the periderm; most features of its histogenesis resemble those that have been described for the epidermis of adult squamates, but certain previously ignored organelles, including possible earlier ß-keratin precursors, are reported. Different strategies regarding in ovo peridermal loss and posthatching shedding behavior are described and discussed in light of presently available data concerning control of cell differentiation in the squamate epidermis.

Thyroid and skin-shedding in the rat snake (Ptyas korros).

Epidermal-thyroid relationships were studied in thyroidectomized (Tx) Ptyas korros kept at 23 degrees C by observing changes in shedding frequency (SF), body weight, oxygen consumption rate (OCR), and postsurgical survival. Tx animals showed increased SFs but lost weight and eventually died, as did Tx animals receiving 3-mono-iodotyrosine injections. However, injections of 3, 5-diiodothyronine inhibited shedding and the animals survived longer. OCRs were similar in all control and experimental groups. It is concluded that among thyroid secretions, only iodothyronines inhibit shedding. Snake shedding is concluded not to reflect general metabolic status as it does in lizards.

The effects of androgens on the ß-glands of the tokay (Gekko gecko): Modification of an hypothesis.

Study of the posterior abdominal epidermis in hypophysectomized/thyroidectomized male and female tokays following surgery, and subsequent androgen therapy, indicates that, contrary to a previous model, all aspects of ß-gland differentiation are under direct androgenic control. On the other hand, another epidermal specialization, the digital foot-pad, shows a pattern of histogenesis directly comparable to that of ß-glands, but is unaffected by androgens. These data are discussed with respect to the evolution of glandular epidermal specializations in gekkonid lizards and the possible role of androgens in modifying the control of cell differentiation in lizard epidermis.

Lizard and newt tail regeneration: a quantitative study.

Almost perfect fits of the Gompertz equation to the growth in length of tail regenerates in the lizard, Lacerta lepida, and the newt, Notophthalmus viridescens, were obtained. Comparison of certain parameters of the equation with published mitotic index data suggests that the Gompertz equation characterizes each system at least from the time that significant mitotic activity is first observed histologically. An objective method for comparing the regeneration periods of the two species is described and applied. A unified hypothesis derived from consideration of properties of the Gompertz equation successfully accounts for the following phenomena reported, but previously unexplained, in the literature: (1) proximal amputations result in longer regenerates than do distal amputations; (2) proximal amputations elicit greater absolute rates of elongation (in mm/day) than do distal amputations; (3) the percent replaced of the length removed is rather constant, regardless of the absolute length regenerated; and (4) one of the parameters of the Gompertz equation appears to be lognormally distributed in a regenerating population. (See text for references.) A computerized interactive graphical system for normalizing growth equations of individual regenerates and integrating the mathematical model with potential candidates for biological control factors is briefly described.

The differentiation of the columella in avian embryos treated with hadacidin with some observations on other skeletal abnormalities.

Single doses of N-formyl hydroxyaminoacetic acid (hadacidin) were injected into chick embryos HH stages 5-30. Embryos surviving for 8+ days total incubation time were recovered and examined for gross and microscopically observable defects. Particular attention was paid to the development of the columella. Survival was only 20%, but a high incidence of cranio-facial and hind limb defects was observed in most age groups. While three categories of columella defect were observed, reflecting some degree of age dependency, this chondrogenic tissue is less susceptible to teratogenic action than other skeletal tissues. The types of columella defect observed are interpreted in the light of a model of cellular interactions in fenestra vestibularis differentiation presented previously. It is concluded that hadacidin produces abnormalities of skeletal differentiation by disrupting morphogenetic, rather than the initiative phases of development of particular elements.

Epidermal regeneration and percutaneous water loss following cellophane stripping of reptile epidermis.

The histological and physiological effects of the removal of superficial corneous epidermal materials have been studied in several squamate species and a caiman. The gross and microscopic anatomy of the squamate integument has characteristics which make cellophane stripping inherently variable, but in general, when corneous materials were removed, they are replaced over a period of one to two weeks, by a tissue with the histological characteristics of the normal alpha-layer. This tissue may be produced by stimulated germinal activity and/or metaplasia of the other presumptive cell populations. In caiman, the thickness of the corneous tissues of the outer scale surface is reduced by stripping and the tissue is restored to normal in approximately two weeks by stimulated germinal proliferation. Measurements of cutaneous water loss (CWL) before, immediately after, and during two weeks post-trauma revealed the following. There is a sudden rise in CWL immediately after stripping, and values decline over the next two weeks as the corneous tissues are replaced. The results are interpreted as indicating that, as in mammals, the impermeability of the epidermis depends on the thickness of the corneous materials. In squamates it appears that the physiological barrier is the alpha-layer of the epidermal generation, and while the beta-layer cannot be excluded as playing some role in reducing the permeability of the integument, its role appears to be primarily mechanical.

A histological study of the development of the avian middle ear and tympanum.

The development of the middle ear and tympanum of Gallus gallus has been studied in embryos Hamilton-Hamburger stages 20-46. Particular attention was paid to the pattern of expansion of the pharyngeal pouch forming the tympanic cavity, and the histogenesis of the tissues of the region of the vestibular window. It is concluded that pouch expansion is brought about by simple epithelial growth into regions devoid of mesenchyme. The mesenchyme does not show significant cell death, but differentiates as connective tissue, macrophages, and sinus vascular spaces. The epithelium of the mature cavity is of endodermal origin, and there is no indication of celomic contributions. We provide a detailed morphological analysis of the development of the footplate from cells of both the second visceral arch and the otic capsule. These detailed observations on the patterns of chondrification of columella and capsular tissues permit the presentation of a model for cellular interactions leading to the differentiation of the annular ligament.

A histological study of the long-term response to trauma of squamate integument.

Scale neogenesis following excision of pieces of skin of various sizes and shapes has been studied in several squamate species. In small wounds, neogenesis does not occur, the wound region contracts, and increased areas of hinge differentiation are seen. In large wounds, the time taken for neogenesis to occur, and the size, shape, distribution, and number of the reformed units, are variable. We confirm previous reports that neogenesis accompanies a renewal phase of the shedding cycle, and suggests that this is because both types of morphogenesis require germinal stability. All types of trauma thus far studied show the initial formation of a hyperplastic wound epithelium with the histological characteristics of a normal α-layer: such tissues are the basis for physiological barrier functions. The mechanical functions of the skin can be fairly adequately restored even by abnormal neogenic scales. The observed variability in the process of scale neogenesis, and the final form of the individual units, are argued to be the result of mechanical factors impinging on the differentiating tissues.

Growth and differentiation of skin.

During the past 25 years, attention has turned from the morphologic aspects of skin development which are well known, to the mechanisms that control this development. Although our knowledge of these mechanisms is still limited, some avenues of investigation appear promising, e.g., epithelial-mesenchymal interactions, cell communication and other cell surface phenomena, and certain aspects of the proliferative process. In the analysis of what controls growth and differentiation, skin, as the experimental system, has played a major role.