Integumentary Development

The integumentary system is made of the skin and associated glands, hair follicles, and nails. The skin is largest organ of the body measuring about 2² meters and weighing about 3.35 kilograms. It covers the entire external surface of the body and plays crucial roles in protection, temperature regulation, and sensation. It develops from the ectoderm, mesoderm, and the neural crest. The ectoderm gives rise to the epidermis. the nails, and hair follicle, whereas the mesoderm gives rise to the dermis and dermal sheath of the hair follicles. The neural crest give rise to melanocytes, the melanin-producing cells in the skin.

Fig. 16.1. The illustration shows components of the skin including the epidermis, the papillary dermis, and the reticular dermis. In addition, it shows skin appendages including a hair follicles, a sweat gland and a sebaceous gland. The dermis has a rich supply of blood vessels, nerves and nerve endings.

 Epidermis

The epidermis is outer layer of skin; it develops from the ectoderm in stages known as the stages of epidermal specification, commitment, stratification, terminal differentiation, and appendageal growth. These stages reflect the differentiation of ectodermal cells into keratinocytes at different stages of differentiation. Epidermal specification occur in the first few weeks of embryonic development where the single layer of flattened ectodermal cells differentiates into a superficial layer called the periderm and a deeper layer called the basal layer. The periderm keratinizes and participates in the formation a protective surface coat known as the vernix caseosa. The vernix caseosa which covers the fetal epidermis has several protective functions and a variable composition. It has a high-water content largely present within cells of the stratum corneum. In the following stages of ectoderm development which are known as the stages of stratification and differentiation, cells of the basal layer proliferate yielding numerous cells called keratinocytes. The newly formed cells are pushed upwards resulting the formation several new layers, a process known as stratification.

Fig. 6.2.  The illustrations show the development of the single epidermal cell layer into a double layered epidermis and the formation of a stratified epidermis by the process of stratification.

As they are pushed upwards, the keratinocytes differentiate and become maturer. Stratification and differentiation results in the formation of distinct epidermal layers known as the stratum basale, the stratum spinosum and stratum granulosum. In the stage of terminal differentiation, cells of the stratum granulosum transform into cornified cells form a waterproof superficial layer called the stratum corneum. Many of the cells of the stratum basale maintain their primitive undifferentiated state and remain within this basal layer as epidermal stem cells. These stem replicate themselves continuously, renewing themselves and the epidermis.

In addition to keratinocytes the epidermis contains Langerhans cells and melanocytes. Langerhans cells develop hemopoietic and monocytes and migrate to skin to reside the middle layers of the epidermis. Melanocytes are of neural crest origin; they develop from neural crest cells lying between the dermomyotome and the surface ectoderm. They then migrate to populate the embryonic skin as proliferating melanoblasts. These melanoblasts are unpigmented containing only immature melanosomes without functional tyrosinase (TYR), the enzyme required for melanin synthesis.

A number of signaling molecules and growth factors produces in the underlying mesenchyme – future dermis – induce and modulate the process of epidermal cell proliferation and differentiation.  

Fig. 16.3.  The illustrations show layers of a fully developed epidermis. Stem cells in the stratum basale proliferate and differentiate as they migrate upwards forming stratum spinosum, graulosum, and corneum. Melanocytes and a Langerhans cell are also present.

The Dermis

The dermis originates from the mesenchyme that underlies the developing epidermis.  It is recalled here that the mesenchyme underlying the epidermis has different origins in different parts of the body. Thus, in the body wall and limbs it originates from the lateral plate mesoderm, in the back region its derived from the paraxial mesoderm, in the head and neck region it originates from the neural crest. The mesenchymal cells differentiate into fibroblasts which synthesize and secrete collagen fibers, elastic fibers, and the ground substance of the dermal connective tissue. The connective tissue of the dermis differentiates into two layers, a superficial loose connective tissue forming the papillary layer and a deeper denser connective that forms the reticular layer of the dermis. 

Anomalies of the skin include aplasia cutis, melanocytosis, and Goltz syndrome. Aplasia cutis is characterized by the absence of the skin that results from the failure of the epidermis to develop properly into an epidermis and dermis. Dermal Melanocytosis (Mongolian Spots) appears as areas of increased pigmentation of the dermis, often affecting the lumbosacral region due abnormal embryonic migration and development of melanoblasts. Goltz syndrome is a rare condition of skin hypoplasia, accompanied by hyperpigmentation or hypopigmentation.

Skin Appendages

The skin appendage include the hair, sebaceous gland, sweat glands, mammary glands, and nails; they develop essentially from the epidermis.

Hair Development

 Hair development begins with proliferation of the basal layer cells of the epidermis forming focal epidermal thickenings known as the hair placodes.  The placode cells proliferate and bulge downwards from the epidermis forming hair buds. The hair buds elongate and penetrate down into the underlying dermis. At their terminal ends, hair buds expand to the form the hair bulbs which invaginate to form  the hair papillae. These invaginations are rapidly filled with mesoderm in which vessels and nerve endings develop. Soon, cells in the middle of the hair buds become spindle-shaped and keratinize to forming the hair shaft. These morphogenetic processes lead to the formation of the hair follicle that comprises the hair bulb, the hair shaft and the surrounding coverings.

The peripherally located cells of the hair bud change shape differentiate into the epithelial hair sheath. Mesenchymal cells surrounding the epithelial root sheath differentiate into the dermal root sheath. Some other mesenchymal cells in the vicinity differentiate into smooth muscle fibers that organize into a bundle extending from the dermal root sheath towards the epidermis forming the arrector pili muscle. Continuous proliferation of epithelial cells of the hair bulb pushes the hair upwards.

By the end of the 3^rd month, the first hairs emerge above the surface the epidermis; this takes place in the region of the eyebrow and upper lip. The first hair to appear is called the lanugo hair and is shed off after birth and is replaced by permanent coarser hairs that develop from new hair follicles. Sebaceous glands arise as lateral outpocketings of the epithelial wall of the hair follicle (Fig. 21.3C). Cells from these buds form the sebaceous glands, which produce sebum by a holocrine mode of secretion.

Hair follicle development is induced and maintained by signals exchanged between epithelial cells of the epidermis)and mesenchymal cells of the dermis; Wnt, hedgehog (Hh), bone morphogenetic proteins (BMPs), and fibroblast growth factors (FGFs), initiate and orchestrate the formation and differentiation of hair follicles.

Fig. 16. 4. The illustrations show the stages of development of the hair follicle and associated sebaceous gland and arrector pili muscle.

Development of Sweat Glands

Sweat glands are exocrine glands confined to the skin; they pass their secretions which is known as sweat via ducts onto the surface of the skin epidermis. Sweat glands are also called sudoriferous glands. They play important roles in the regulation of body temperature by secreting a water sweat, which evaporates at the surface the skin thus colling it. There are two main types of sweat glands, namely the eccrine sweat glands and apocrine sweat glands.

Eccrine sweat glands release their watery secretion by the merocrine mode of secretion where the secretion of the secretory cells is released into the lumen by exocytosis without loss of any part of the cell. Eccrine sweat glands are present in the skin all over the body but are more concentrated in the skin of the palms, soles, forehead, and armpits. Their primary function is thermoregulation and their activity is induced by heat, physical activity and emotions. The sweat produces by these glands is releases on the surface of the skin.

Apocrine sweat glands on the other hand, are characterized by an apocrine mode of secretion where the secretory material accumulates in the apical portion of the secretory cell which then pinched off and passes into the lumen when fully filled with the secretory material. Thus, their secretion is thicker than the watery sweat produced by the eccrine sweat glands. This type of sweat glands is present in the armpits and around the external genitalia. Their secretion passes into hair follicles and via hair follicles on the skin surface. Their secretion is odorless at first but often develops an odor when cracked down by bacteria present on the skin. Apocrine sweat glands are activated by emotional stress and sex hormones. The mammary glands, Moll of the eyelids, and the ceruminous glands of the auditory meatus which produce the ear wax, are modified apocrine sweat glands.

Fig. 16.5. Illustrations of an apocrine sweat gland (left) and an eccrine sweat gland. The duct of the apocrine sweat gland opens onto the surface of the epidermis via the hair follicle, whereas the duct of the eccrine sweat gland opens directly onto the epidermal surface.

Eccrine sweat glands develop from the epidermis of the skin in the 4^th month of gestation. To begin with, the epidermal cells proliferate and form focal thickenings known as placodes. Each placode develop into and eccrine glad bud that grows into the underlying dermis and elongates forming primordial sweat gland ducts. Each primordial duct elongates and coils, and its distal part differentiates into the coiled tubular secretory unit. Eccrine sweat glands are not fully functional until after birth.

Apocrine sweat glands are confined to the axilla (armpit), perineal region and in the areola around the nipple.  Apocrine sweat glands also are ectodermal in origin and develop from the same epidermal buds that give rise to hair follicles. Accordingly, the have no pores opening onto the epidermal surface; instead, their duct opens into the hair follicle and it is via the hair opening that its secretion reaches the skin surface. Entrance of apocrine duct into the hair follicle occupies a position more superficial than the entrance of the sebaceous gland, accordingly the secretion is a mixture of sweat and sebum. Apocrine sweat glands do not function until hormonal stimulation during puberty; before puberty they are small and inactive. The hormonal changes that take place at puberty trigger further enlargement of the gland differentiation of its secretory cells into active cells that synthesize and secrete a viscous milky sweat.

Fig. 16.6.  The illustration shows confluence of the apocrine duct with the hair follicle at a level higher than the sweat gland; the eccrine sweat gland duct opens onto the surface independent of the hair follicle via its spiral intraepidermal portion, acrosyringium.

Development of the Mammary Glands

The mammary glands are modified sweat glands that begin to develop in the 7^th week of embryonic development as bilateral bands of epidermal thickening known as the mammary ridges or mammary ridges. At this stage, each ridge or line extends on each side of the body from the level of the forelimb to the region of origin of the hind limb. The greater part of each mammary ridge disappears shortly after its appearance. The remaining part of the ridge persists in the thoracic region, enlarges and develops into the underlying mesenchyme (dermis) forming about twenty small solid buds. These buds elongate and form solid cords that canalize and form lactiferous ducts that open together into a small epithelial pit that transforms shortly after birth into a nipple. At puberty, and under the influence of female sex hormones the distal ends of the ducts proliferate, branch, and differentiate forming mammary gland alveoli. In males, the mammary glands as in females, develop from the mammary gland buds but they soon regress and remain rudimentary.

Fig. 16. 7.  The illustration on the left shows the two mammary ridges (milk lines), one on each side of the body. The illustration in the middle shows the appearance of the mammary ridge in cross section (above), and its development into branched lactiferous ducts (below) from the mammary bud. The illustration on the right shows the structure of the fully developed female mammary gland (breast).

Congenital anomalies of the mammary glands include amastia, amazia, athelia, polythelia, polymastia, and hypoplasia. Amastia is the complete absence of the mammary gland that results from disruption in the development of the mammary ridges due to genetic or chromosomal abnormalities, whereas amazia is the absence of mammary gland tissue in the presence the nipple and the areola.  Athelia is the absence of the nipple and areola in the presence of the glandular tissues of the breast. Polythelia on the other hand is presence of more than one nipple on each side of the body, often along the milk line. Polymastia is the presence mammary gland tissue in more than one location along the milk line, whereas hypoplasia is the presence of breasts that are much smaller than normal and is caused by underdevelopment of the mammary buds.

Fig. 16.8. The woman on the left has amazia (absence of mammary glands in the presence of nipples). The illustration shows mammary abnormalities along the milk line including presence additional breasts or mammary glands (polymastia) and presence of additional nipples without accompanying mammary glands (polythelia).

Take a quiz