The stratum corneum is the outermost layer of the epidermis, and is made up of 10 to 30 thin layers of continually shedding, dead keratinocytes. The stratum corneum is also known as the "horny layer," because its cells are toughened like an animal's horn.
As the outermost cells age and wear down, they are replaced by new layers of strong, long-wearing cells. The stratum corneum is sloughed off continually as new cells take its place, but this shedding process slows down with age. Complete cell turnover occurs every 28 to 30 days in young adults, while the same process takes 45 to 50 days in elderly adults. The dermis is located beneath the epidermis and is the thickest of the three layers of the skin 1.
The main functions of the dermis are to regulate temperature and to supply the epidermis with nutrient -saturated blood. Much of the body's water supply is stored within the dermis. This layer contains most of the skins' specialized cells and structures, including:. The upper, papillary layer, contains a thin arrangement of collagen fibers. They differ in color and the way of synthesis. Melanin has numerous properties which are beneficial to the body: UV light absorption and scattering, free radical scavenging, coupled oxidation-reduction reactions and ion storage [ 23 , 38 , 39 ].
The availability of substrates and the function of melanogenesis enzymes decide about the types of melanins produced Figure 4. In the presence of cysteine DOPAquinone react with it, yielding 3- or 5-cysteinylDOPAs, which then oxidize and polymerize, giving rise to yellow-red soluble melanin — pheomelanin [ 37 , 41 ].
In the absence of thiols cysteine, glutathione or thioredoxin brown-black eumelanin is produced. Human skin contains a mixture of all melanin types, and the ratio of those in part determines visible pigmentation [ 19 ]. Diversity of skin pigmentation among different ethnic groups is preserved and depends on eumelanin content.
The ratio of eumelanin to total melanin decide about skin color [ 30 ]. Pheomelanin does not correlate with skin pigmentation, a similar amount of this pigment is observed in the dark and light skin. While in hair, the ratio of eumelanin to pheomelanin decides about the color [ 35 ]. Eumelanin comparing to pheomelanin has better photoprotecting properties — higher resistance to degradation and ability to reactive oxygen species ROS neutralization [ 44 ].
Eumelanins are considered to be more effective in terms of photoprotection than the reddish pheomelanin. As a consequence, the risk of skin cancer in lighter skin is fold higher than in the darker one [ 41 ]. Products of genes regulating melanogenesis act at subcellular, cellular, tissue and environmental levels [ 21 ].
During melanogenesis, as intermediate products, cytotoxic molecules are synthesized quinones, hydrogen peroxide. Thus, melanocyte protects itself by separating areas of melanogenesis in melanosomes and increases the level of antiapoptotic protein Bcl-2 [ 1 , 21 ]. Simplified scheme of the melanin synthesis in melanocytes during melanogenesis. Tyrosine under influence of the basic enzymes such as tyrosinase TYR , tyrosine- related protein 1 TYRP1 and 2 TYRP2 changes into a polymer of melanin, a mixture of pigments named eumelanin black-brown and pheomelanin yellow-red.
Melanosomes probably originate from endoplasmic reticulum of melanocytes, but it still remains a matter of debate [ 25 ].
Of these three enzymes, tyrosinase is crucial to melanogenesis and is synthesized on the ribosomes of the RER and transported to the Golgi complex where it undergoes glycosylation, which is a process essential for its normal structure and function [ 45 , 46 ]. There are four stages in melanosome development Table 2. Premelanosomes Stage I are a round, small vesicles with an amorphous matrix. Melanosomes at Stage II have an organized, structured fibrillar matrix mainly from gp family and tyrosinase is present but pigment synthesis has not been noted.
The beginning of melanin production takes place at Stage III, where pigment is deposited on protein fibrils. At the last Stage IV pigment fills the whole melanosome [ 41 , 47 ]. Fully melanized melanosomes lose tyrosinase activity and are transported to surrounding keratinocytes by elements of the cytoskeletal system Figure 1 [ 48 ]. Characteristics of the developmental stages of melanosomes during melanin synthesis. The melanogenesis takes place in special organelles named melanosomes.
The melanosome produces melanin, which polymerizes and settles on the internal fibrils Stage III. In the last stage Stage IV melanosome is filled up with melanin. The precise mechanisms that control the organization and number of melanocytes in the epidermis are unknown although keratinocytes may interact with melanocytes via growth factors, cell surface molecules, or other factors related to proliferation and differentiation of the epidermis.
Melanocyte is a highly differentiated cell that produces a pigment melanin inside melanosomes. This cell is dark and dendritic in shape.
Melanin production is the basic function of melanocyte. With the process of differentiation this cell loses the proliferative potential. Epidermal melanocytes are thought as a very stable population which proliferate extremely rarely under normal circumstances.
The MITF as the main melanocyte transcription factor influences proliferation, dendrite formation, melanin synthesis and induces the expression of antiapoptotic bcl-2 gene [ 50 ]. Epidermal melanocytes are long-living cells while hair melanocytes live as the hair cycle lasts median: years [ 31 ]. Density of melanocytes in the skin depends on the environment mainly UVR and factors secreted by keratinocytes and fibroblasts. In the older people, apart from a decreased number of melanocytes morphology is changed melanocytes are larger, more dendritic and tyrosinase activity is reduced [ 19 , 31 , 52 ].
The relationships between ageing and the proliferative activity of melanocytes have been observed. In vitro , adult melanocytes proliferate less times than fetal and neonatal melanocytes [ 53 ].
Also, melanocytes from patients with a premature ageing disorder have reduced proliferative potential [ 50 ]. Terminally differentiated melanocyte proliferative potential is inhibited by changes in the cell cycle control elements, e.
Table 3 lists basic cell cycle regulators involved in the regulation of melanocytic senescence based on [ 53 ]. The basic activity of the cell cycle regulators and other factors associated with melanocytes senescence. Furthermore, the reason for a decreased number of melanocytes is programmed cell death of terminally differentiated cells. In the melanocyte proliferation, the mitogen-activated protein kinase MAPK pathway is involved, which is stimulated by many growth factors.
In the terminally differentiated melanocytes this main proliferative pathway is not active [ 50 ]. Discoveries in the field of molecular regulations of melanocyte proliferation and death help us understand disorders such as melanoma or vitiligo [ 54 , 55 ].
Summarizing, the proliferation and differentiation of melanocytes during development are regulated by different genetic and epigenetic factors derived from keratinocytes, fibroblasts, melanocytes, the pituitary gland, other organs and environmental factors such as UV radiation [ 24 ]. Neural Crest Cells is a group of cells originating from the embryonic germ layer named ectoderm. Under inductive influence of the notochord, the middle area of the embryonic disc differentiates into neuroectoderm that is visible as a neural plate at 4-week-old human embryo Figure 5A.
This plate folds and changes into the neural tube, future central nervous system elements — brain, spinal cord. These neuroectodermal cells migrating to many places of the forming embryo's body are neural crest cells — NCC Figure 5C. Neural crest cells are initially multipotent cells but gradually become lineage-restricted in developmental potential.
This potential is determined by anatomical localization along the cranial-caudal axis, e. These cells proliferate and start to express distinct molecular markers [ 7 , 56 ]. Development of the neural crest cells NCC during early embryogenesis at a 4-week-old embryo from neuroectoderm.
The neuroectodermal cells proliferate, form the neural plate that folds, fuses and changes into neural tube A , B. During this neurulation process, cells from edges crests of the neural plate separate from the neural tube as independent population of embryonic cells named neural crest cells, that is located above the neural tube future brain and spinal cord and beneath surface ectoderm future epidermis C.
Dorsally migrating trunk NCC move between the surface ectoderm and somites, finally develop into melanocytes of the epidermis and hair A. Ventrally migrating trunk NCC move between the neural tube and somites, give elements of the peripheral nervous system ganglionic cells, Schwann cells , medulla of the adrenal glands and according to latest investigations, melanocytes of the skin A.
Neural crest cells are traditionally grouped into four regionally distributed populations: cranial, vagal, trunk and sacral. Melanocytes mainly origin from cranial and trunk-located NCC. Melanocytes residing in skin of the head origin from the cranial NCC while in the remaining parts of the human body mainly from the trunk NCC. Except melanocytes, cranial NCC together with mesodermal cells form the ectomesenchyme of the head, that gives skeleton, muscles and dermis of the head Figure 6B [ 57 ].
According to embryonic migratory pathways, the trunk NCC is divided into two populations, dorsally between surface ectoderm and somites and ventrally between neural tube and somites migrating cells Figure 6A. Traditionally, the dorso-laterally migrating cells are thought to be the main source for melanocytes while the ventrally migrating cells give rise to the peripheral nervous system and adrenal medulla Figure 6B.
But, there is strong evidence that a fraction of melanocytes arise from cells migrating first ventrally and then along the nerves [ 9 , 58 ]. Cells present in a nerve sheath Schwann cells have the potential to produce melanocytes also after birth.
In vitro , Schwann cells cultured in melanocytes medium de-differentiate into glial-melanocytic progenitor able to give melanocytes [ 59 ]. Thus, cells migrating ventrally either differentiate into neurons or are maintained as multipotent cells that differentiate into cells forming myelin sheath or melanocytes Figure 6 [ 7 ].
These cells invade the epidermis during the process of embryonic cutaneous innervation [ 9 ]. The recent findings that congenital prenatal nevi begin as intradermal nevi seems to support the hypothesis that precursors for melanocytes could origin from dermis cells [ 60 ]. It is suggested that prenatal nevi may develop from the precursors for Schwann cells, which arrive near epidermis along cutaneous nerve, may respond to factors secreted by epidermal cells and differentiate into melanocytes.
As cutaneous nerves grow from deep dermis near the epidermis they branch and form the candelabra pattern a neurocutaneous unit. Along these branches precursors for melanocytes migrate to the epidermis and as a result the congenital nevi may develop [ 60 ].
During human development, melanoblast migration and cutaneous nerve growth take place at the same time between 6 and 8 weeks [ 9 , 60 ]. Communication between the nervous system and epidermal melanocytes has been proven [ 61 ]. The observation that epidermal melanocytes molecularly differ from dermal melanocytes seems to support the hypothesis about double origin of skin melanocytes [ 62 ].
Thus, melanocytes in the skin either derive directly from NCC populating the skin via a dorsolateral migratory pathway or arise from ventrally migrating precursors forming the myelin around the cutaneous nerves [ 63 ]. As melanoblasts travel through the dermis, they multiply. While traveling to their final destinations, melanoblasts sequentially express additional melanogenic genes, many of them regulated by transcription factor MITF.
The most important in the maturation of melanocyte is the appearance of tyrosinase, enzyme of melanin synthesis. Melanocytes finally reside in the skin and hair follicles, the oral mucosa, the choroid of the eye, the iris, and some internal sites, such as meninges and the inner ear the stria vascularis. The fate of NCC depends on environmental factors they meet on the migratory pathways [ 7 ]. After cell specification, melanoblasts proliferate and spread to their final destinations in the epidermis and hair follicles where they differentiate.
It takes place at weeks and by weeks the majority are localized in the epidermis [ 60 , 64 ]. Whether all of them reach the epidermis is an unresolved developmental problem. Dermal melanocytes are seen during human fetal development but they are not evident after birth. There are suggestions that some melanoblasts could stay in the dermis [ 64 , 65 ]. It remains unknown how the stream of melanoblasts to the epidermis is controlled.
The time when melanoblast presence in the dermis is detectable is also time for cutaneous nerve development [ 60 ]. On the 18 th week of intrauterine life a hair which comes through the skin surface have melanocytes present in the hair bulb [ 64 , 66 ] but the activity of tyrosinase is very low [ 67 ]. You can also see how the prickle cells in the stratum spinosum layers, appear to have a veil of melanin over the nucleus.
Melanocytes make the pigment called melanin. Tyrosine is converted into dihydroxyphenylalanine DOPA which is then polymerised into melanin. Melanocyte: Cross-section of skin showing melanin in melanocytes.
The deepest of the epidermal layers is called the stratum basale or stratum germinativum. In this layer lie important cells called melanocytes. Their name is derived from two parts: melano-, which means black or darkness, and -cyte, which means cell. Melanocytes are irregularly shaped cells that produce and store a pigment called melanin. The most abundant type of melanin is called eumelanin.
This pigment is stored in organelles called melanosomes. Eumelanin is responsible for the brown and black pigmentation of human skin or the lack thereof if little of it is produced. The production of melanin is called melanogenesis—genesis means formation or development.
Regardless of background, every person has largely the same number of melanocytes, but the genetics of each person is what determines how much melanin is produced and how it is distributed throughout the skin.
For example, light skinned individuals may have darker places like nipples and moles. Conversely, dark skinned individuals have a lighter tone to the palms of their hands. Another critical factor, exposure to sunlight, triggers the production of melanin as well. This is what gives us a tan. People with darker skin have more active melanocytes compared to people with lighter skin. However, the pigment of our skin also involves the most abundant cells of our epidermis, the keratinocytes.
While melanocytes produce, store, and release melanin, keratinocytes are the largest recipients of this pigment. The transfer of melanin from melanocytes to keratinocytes occurs thanks to the long tentacles each melanocyte extends to upwards of 40 keratinocytes. Tanned Skin: Exposure to UV radiation through tanning causes changes in the pigmentation of the skin by increasing melanin production.
Privacy Policy. Skip to main content. Integumentary System. Search for:. The Skin. Learning Objective Identify the layers of the skin. Key Takeaways Key Points The outer layer of skin, the epidermis, provides waterproofing and serves as a barrier to infection.
The inner layer of the skin, the subcutis, contains fat that protects us from trauma. Key Terms epidermis : The outermost layer of the skin. Learning Objective Describe the layers of the epidermis. Key Takeaways Key Points The epidermis provides a protective waterproof barrier that also keeps pathogens at bay and regulates body temperature.
The main layers of the epidermis are: stratum corneum, stratum lucidium, stratum granulosm, stratum spinosum, stratum germinativum also called stratum basale.
Keratinocytes in the stratum basale proliferate during mitosis and the daughter cells move up the strata, changing shape and composition as they undergo multiple stages of cell differentiation. Those keratinocytes found in the basal layer stratum germinativum of the skin are sometimes referred to as basal cells or basal keratinocytes.
Learning Objective Differentiate among the regions of the dermis and the hypodermis. Key Takeaways Key Points The dermis is divided into a papillary region and a reticular region.
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