Introduction The skin is the

Introduction The skin is the largest organ in mammals. It covers the surface of the body and consists of three main layers: the surface epidermis, the subjacent dermis, and the subcutaneous tissue (the lowest layer). An important function of the skin is to protect an animal\'s body from external stimuli. The skin consists primarily of three cell types: keratinocytes, melanocytes, and fibroblasts. Keratinocytes compose the bulk of the epithelium, undergo keratinization, and form the dead superficial layer of the skin. These superficial keratinized order AZD-4547 continuously desquamate from the surface and are replaced by cells derived from mitotic cells in the lowest layer of the epidermis (i.e., the basal layer). The higher level cells are successively displaced by the population of new cells below them. As they move upwards, they elaborate keratin and accumulate it in the cytoplasm, and finally the cells are mostly occupied by keratin. Melanocytes, which are pigment-producing cells, are originally derived from neural crest cells in the embryonic skin. Neural crest cells migrate from the dorsal to ventral side and localize all over the body. Melanoblasts, which are a precursor of melanocytes, differentiate from the neural crest cells, proliferate, and colonize the epidermis in the embryonic stage. In the epidermis, the melanocytes locate in the basal layer and do not keratinize, but they can produce melanin pigments. Mammalian hair forms from hair follicles derived from hair germ cells that begin as an epidermal invagination, and include keratinocytes, melanoblasts, and melanocytes. The dermis, which consists of fibroblasts, forms a thickening beneath the epidermis and the end of the invagination surrounds the thickening. The dermal thickening develops into a dermal papilla, and the surrounding part of the invagination forms the hair bulb. The lower half of the hair bulb is called a hair matrix, and numerous functional melanocytes are localized there. Keratinocyte stem cells and melanocyte stem cells locate in the bulge area of hair follicles (i.e., at the site of attachment of the arrector pili muscle). They produce new proliferating and differentiating keratinocytes and melanocytes.
Structure and function of the epidermis The epidermis is a histologically stratified squamous epithelium and constantly requires renewal from birth to death. An important role of the epidermis is to protect the skin from many types of environmental stresses such as exposure to bacteria; viruses; chemicals; UV radiation; ionizing radiation; electromagnetic waves; and physical, thermal, and mechanical injuries (i.e., barrier function). Keratinocytes compose the bulk of the epidermis, undergo differentiation (i.e., keratinization), and form a dead superficial layer on the skin (this layer is called the “keratinized layer” or “cornified layer”). A function of keratinocytes is to produce keratin and filaggrin, which are involved in regulating the barrier function. The renewal of the epidermis is supported by the proliferation and differentiation of keratinocytes (i.e., epidermal homeostasis primarily depends on a balance between the proliferation and differentiation of keratinocytes). Mammalian melanocytes locate in the basal layer; they do not keratinize but produce melanin pigments. Melanin is produced from l-tyrosine (L-Tyr) with the aid of enzymatic reactions by tyrosinase (Tyr), Tyr-related protein (Tyrp)-1, and Tyrp2. Most epidermal melanocytes migrate to the hair follicles and colonize hair matrix melanocytes in hairy general body (i.e., trunk) skin in animals. In the glabrous skin of the ear, nose, foot, and tail in animals and in human skin (except for the scalp, underarm, and pubic skin), numerous differentiated melanocytes are present in the epidermis—even in adults. However, in the epidermis of hairy skin in mice, epidermal melanocytes exist only during the early weeks after birth. In human skin, the epidermal melanin unit, which comprise keratinocytes and melanocytes, has a key role in regulating pigmentation and homeostasis of the epidermis.