THE SKIN AND ITS DERIVATIVES

PERCIVAL P. SANGEL, D.V.M.,M.Sc.

Instructor Department of Biology School of Science & Engineering Ateneo de Manila University Lecture: BI 132

Vertebrate Integument: consists of ectodermally derived epidermis resting upon a layer of connective tissue called the dermis as they mature, developing epidermal cells produce increasing amounts of specialized intracellular protein called keratin both development and maintenance of the skin and its appendage involves a series of communications between the ectoderm and the underlying mesenchyme

Early Development of the Integument: Initially, the embryo is lined by a single layer of ectodermal cells which is not closely associated with the underlying mesenchyme but rests upon a loose layer of extracellular matrix. Major changes occur in the early ectoderm First, it begins to stratify into two layers: a deep layer of basal ectoderm cells and a newly forming superficial layer, the periderm which covers the surface of the amniote embryo before the ectoderm is transformed into a welldifferentiated epidermis. Second, the appearance of a well-defined basal lamina beneath the basal layer of the ectodermal cells

 Formation of the dermis lags behind differentiation of the epidermis. Dermis arises from the following: 3 mesodermal and 1 ectodermal origin 1. Dermis of the dorsal body wall originates from dermatomes of the somites according to a strict segmental arrangement 2. Dermis of the ventral body wall and extremities is derived from the lateral mesoderm 3. Dermis of the cranial region arises from somitomeric mesoderm 4. Dermis of the face and ventral neck is derived from the cranial neural crest ectoderm

Integument - Structure and Development

Epidermis
Stratified, squamous Ectoderm

Basement Membrane
Fibrils

Dermis
Fibrous connective tissue Mesodermal dermatome of the somites

Integument - Structure and Development

Stratum germinativum
Cuboidal Mitotic Division Migrate Distally Differentiate Sloughed off

Synthesis of keratin
Water insoluble protein that fills cells Stratum corneum of Vertebrates

Integument - Structure and Development

Beneath the Basement Membrane (Dermis)
Proximal Migration and differentiation of of collagen fibers and other structures Two layers
Stratum laxum (spongiosum) Stratum compactum

Blood vessels, nerves, pigment cells Endotherms bases of hair and feathers + erector muscles

Interaction between dermis and epidermis

Bony scales Horny scales Feathers Hair Other skin derivatives claws, antlers, horns, baleen Cells that form the skin layers
Respond to inductive influences of adjacent cells and to environmental influences.
Neural crest cells migrating between epidermis and dermis signal the building of these derivatives

Histogenesis of the Skin and its Derivatives: Epidermis The normal adult mammalian epidermis is multilayered structure, the thickness of which varies in the different parts of the body. The basal layer rests upon a basal lamina which separates it from the dermis. The cells of this layer are mitotically active. The progeny of the basal cells become progressively displaced to more superficial layers as additional cells are produced by the dividing stem cells of the basal layer As cells rise toward the surface of the epidermis, they undergo a series of inexorable or unstoppable changes that will result to a flat, nonliving shell full of keratin, the protein that ends the differentiation of the epidermal cells.

Skin A B
4 3

2 Figure 10 A-B. Labiodermal junction of canine lip. A-50X, B-200X. The epidermis in Figure A (inset) is magnified in Figure B. The following layers of the epidermis can be identified: stratum basale (1), stratum spinosum (2), stratum granulosum (3), and stratum corneum(4). Note the presence of pigment granules in the lower layers.

1 1 1

Immigrant Cells in the Epidermis: Three types of foreign cells invade the embryos epidermis and remain there during adult life: 1. Melanoblasts: from the neural crest cells, reach the dermis in human embryos during the second month and penetrate the epidermis early in the third month; differentiate into melanocytes (pigment cells) and associated with the formation of the pigment granules (melanosomes). The number of melanocytes in skin does not differ much from race to race only the pigment per cell in the melanocytes. 2. Langerhans cells: from precursor cells at the bone marrow and invade the fetal epidermis at the end of the 1st trimester; they are not readily distinguishable from ordinary epidermal cells (keratinocytes) but contains distinctive cytoplasmic granules and are readily identified histochemically by their high membrane-bound ATPase or by surface antigen; they process antigens that penetrate the epidermis and cooperate with the T lymphocytes in the epidermis for a cell-mediated immune response.

3. Merkel cells: arrive at the fetal epidermis after the two foreign cell types; may have come from the neural crest cells and become associated with the free nerve terminals and serve as slow-adapting mechanoreceptors for the skin

Hair: In human, hair formation first becomes recognizable over the eyebrows, scalp, lips and chin of embryos and spreads throughout the body in a craniocaudal direction. Hair formation is first seen when a cluster of basal epidermal cells begins to project as a bud downward into the dermis. As the epidermal bud continues to extend downward, a condensation of dermal mesenchymal cells known as the dermal papilla begins to indent the tip. The epidermal hair bulb that partially surrounds the dermal papilla like an inverted cap is the source of the hair itself. Primordia of the hair and its associated structures take shape. The incipient hair is first represented by a cone of rapidly proliferating epidermal cells from the inner wall of the epidermal hair bulb. The growing hair continues to push upward through the center of the hair follicle until it reaches the surface of the fetal epidermis. Fully formed hairs continue to push upward through the canal that they have created within the epidermal follicle.

 As the hair bulb begins to mature, it is infiltrated by melanocytes which provide the pigment that colors dark hair. The melanocytes become more tightly localized at the root of the hair bulb. The epidermal cells that contitute the hair shaft begin to undergo keratinization (during the fifth fetal month in humans). This is marked by the production of hard granules of keratin complex called trichohyalin which gives the hardness to the hair. Two other structures associated with the developing hair follicle. One is the sebaceous gland which begins as a bulge of epidermal cells midway along the length of the follicle. They differentiate to form an oily secretion called sebum which is discharged onto the surface of the skin via the sheath of the hair follicle. Vernix caseosa a protective coating in human fetus composed of whitish material mixed with desquamated epidermal cells. Another s the arrector pili muscle where one of its end is attached to the bulge of epidermal cells along the hair follicle and the other end is embedded in the dermis near its junction with the epidermis. Responsible for raising the fur when the animal gets angry or feeling of goose bumps in humans lanugo are first hairs to emerge over the fetal body

Feathers Like hair, feather begins as concentration of dermal cells beneath an epidermal placode. Originally, flat feather rudiments rises above the surface of the skin as a feather bud. The epidermis at its base sinks down into the dermis to form a pitlike structure called the feather follicle and the rapidly growing feather bud assumes a conical shape. First feathers to appear in the embryo are the down feathers in which the barbs all arise in a circle at the same level from a short shaft. The most prominent feather type in the mature bird is the familiar contour feather. In the development of a down feather, the thickened epidermis of the elongating feather bud forms a series of roughly parallel columns called barb ridges beneath a cornified sheath of surface cells. As the down feather matures, the cells of the dermal pulp retract from the feather bud and the epidermal components harden as a result of keratinization. Final eruption of the down feather occurs when the cornified outer epidermal sheath splits open and allows the barb ridges or columns to spread out in a plumelike fashion to form a definitive down feather barbs which possess regular branching structures called barbules (for insulation)

 Up to the stage of the conical feather bud, the development of the contour feathers is morphologically similar to that of down feathers. At the base of the cone-shaped contour feather bud an epidermal collar produces a series of parallel barb ridges but soon the dorsal part of the epidermal collar begins to elongate to form the long shaft of the feather. Elongation of the feather shaft occurs entirely within the cone of the feather bud and the barb ridges bend beneath the cornified outer epidermal sheath of the feather bud begins to split, the apical part of the shaft and its associated barbs are freed from their conical restraint. the freed barbs unroll and flatten out in a typical feather form, while at the base the barbs are still encased in the intact epidermal hull. erector muscle: smooth muscle that causes the contour feathers to fluff (warmth) ; depressor muscle: smooth muscle that allows the feathers to be flattened (flying)

Scales The initial placodal stages of scale development differ from those of the feather in that there is not a pronounced condensation of dermal cells beneath the placode; however, as the placode elevate into ridges, dermal cells aggregate and proliferate at the apical end of the scale that is beginning to take shape. The apical end of the scale continues to grow until it overlaps the basal portion of the next scale in line. By this point, both the epidermal and peridermal cells covering the inner and outer surfaces of the scale have undergone complex series of differentiative changes and have begun to form keratin specific for each surface of the scale.

Tissue Interactions in Integumentary Development Almost all aspects of integumentary development depend on continuing series of reciprocal communications between the ectoderm and its underlying mesenchyme. One of the simplest ways to test the importance of tissue interactions in skin development is to separate the ectodermal and mesenchymal components and raise them separately. Both failed to develop into epidermis and dermis, respectively. This emphasizes the importance of ectodermal-mesenchymal communication in the normal development of skin.

Heterotropic recombination and instructive induction

Heterospecific recombinations

Dermal-epidermal interactions appear to be simple one-way avenues of communication, with the dermis sending out a location-specific message and epidermis replying with species-specific response. (Sengels proposition) Initial message emanates from the predermal mesenchyme and instruct the overlying ectoderm to form thickened placodes in a region-specific pattern.

 the ectodermal placode sends back a message causing the predermal mesenchyme cells to condense beneath the placodes. The condensed dermis then sends a second class-specific inductive message that is transmitted back to the thickened ectodermal placode. This second dermal inductive message specifies the formation of a specific kind of appendage (contour feather, scales or hair) second dermal inductive signal transmits information that can be translated into both specific form of the appendage and specific keratin proteins by epidermis

Pattern Formation in the Integument Feathers: in avian embryos, feathers form as specific patches of skin called feather tracts (pterylae) while featherless areas are called apteria Feather papilla which populate a feather tract arise in a well-defined and well-controlled sequence. In the tracts that cover the back and neck, the nearly simultaneous appearance of feather primordia in the single row at midline marks the start of the feather tract called primary row. Secondary row of feather papilla arises on either side of primary row. In a regular geometric pattern, the feather germs of secondary row arise in staggered fashion laterally to those of primary row. Feather germs of the tertiary row next form laterally to those of secondary row. The sequence of additional rows continues until the feather tract is filled out.

Epidermal Differentiation Regardless of regional differences, the epidermis all over the body has the same fundamental organization and function. It is a multilayered structure which is almost totally geared toward providing the body with an impermeable protective covering. Cells of the basal layer contain the constellation of cytoplasmic organelles associated with protein synthetic activity. They also contain scattered bundles of 6- to 8- nm-thick intermediate filaments which represent aggregates of subunits of keratin and are characteristic of the differentiating epidermal cell. As the epidermal cells (keratinocytes) are pushed outward with the next layer (stratum spinosum), they develop extensive networks of keratin filaments which converge on the desmosomes, the small patchlike structures that bind one epidermal cell to its neighbor. The outer cells of the spinous layer begin to accumulate another maker of epidermal differentiation, keratohyalin granules.

 Keratohyalin granules are prominent components of the stratum granulosum of the epidermis. By the time keratinocytes have moved out to the granular layer, the nuclei develop the classical signs of terminal differentiation: they become compressed, the nuclear chromatin becomes dense, and the nuclear membrane shows signs of breaking up. keratin subunits that are made in more mature keratinocytes have higher molecular weights than do those synthesized in the basal cells. Keratinocytes next pass through a thin transitional layer, where the nuclei are lost and the cells become noticeably flattened. The cells become little more than flattened bags of keratin filaments which constitute the outer stratum corneum which is held by histidine-rich protein called filaggrin derived from the component of keratohyalin granules secreted at the intercellular spaces.

Pigmentation Pattern in the Skin The myriad colors and patterns one finds in animals of a typical rain forest or coral reef are attributable to a class of cells called chromatophores which originate in the neural rest and from there migrate in well-defined, species-specific patterns to their final peripheral destinations. Three major types: 1. Melanophores: give yellowish-brown, brown, or black coloration because of their melanin or a derivative of melanin 2. Xanthophores: containing carotenoid or pteridine pigments which are responsible for the yellow to red color 3. Iridophores: produce metallic effects (silvery or bluish) because structural elements within the cells reflect light

Mammary Glands First indication of mammary gland development is the appearance of bandlike ectodermal thickening (milk lines) that run from the region of the armpit (axilla) to the groin (inguinal region). Actual number and location of individual mammary glands vary considerably from one species to another, but they are all located somewhere along the length of the milk lines. In humans, the original milk line is a raised ridge of ectodermal cells underlain by a slight concentration of mesodermal cells. As mammary gland development continues, a solid plug of ectodermal cells at the site of the future nipple pushes its way into the subjacent mesenchyme. Soon a cluster of branching ectodermal cords foreshadows the formation of the hollow mammary ducts.

 Initial ingrowth of mammary duct primordia into the underlying mesenchyme is the result of an ectodermal-mesenchyme inductive interaction. The mammary mesoderm is the inductor and the ectoderm is the responding tissue. Two types of mammary mesoderm: fibroblastic mammary mesenchyme that closely surrounds the epithelial duct primordia and a precursor of the mammary fat pad. Interaction with tissue of the mammary fat pad rather than the fibroblastic mesoderm is the major factor that result in the shaping of the characteristic mammary duct system. Although rudimentary ductal tissue persists in human male, the mammary primordia of the male mice disappear early in development as a result of testosterone-induced cell death.

 The male and female mammary epithelial primordia are equally sensitive to the effects of testosterone and testosterone does not act directly upon the ductal epithelium;instead, the effect is mediated through the mammary mesenchyme. Some hormones involved in breast development and lactation: Estrogen Growth hormone Prolactin-inhibiting factor Prolactin releasing factor Prolactin Oxytocin