The skin is the largest organ of the body, covering an area of approximately 2 m2. The skin is composed of the cutis (including the dermis and epidermis), subcutaneous tissue, and skin appendages. The epidermis, which is derived from ectoderm, is the outermost layer of the skin and is mainly composed of keratinocytes. The dermis, which is derived from mesoderm, is located underneath the epidermis and is mainly composed of elastic fibers, type I collagen, and connective tissue. It is formed by the papillary dermis and the reticular dermis. The subcutaneous tissue, which is derived from the mesoderm, is the innermost layer of the skin and is mainly composed of fat and connective tissue. Skin appendages are derived from the skin and include hair, nails, and glands. The main functions of the skin are protection (barrier against ultraviolet radiation, microorganisms, and water loss), the synthesis of vitamin D, detection of sensation (e.g., touch, temperature, pain), and the regulation of body temperature.
The skin is composed of several layers, which are categorized as follows (from superficial to deep):
- Derived from ectoderm
- Primarily composed of keratinocytes, which constantly regenerate approximately every 30 days
- The outermost and nonvascularized layer of the skin that maintains the skin's barrier function
- There are 5 layers of the epidermis, which are categorized as follows (from superficial to deep):
Stratum corneum: outer layer of the epidermis
- Consists of dead (anuclear; ), keratin-filled cells
- This layer is constantly being sloughed off.
- Stratum lucidum: thin, translucent layer
Stratum granulosum: also called the granular layer
- Contains keratohyalin
- This layer has waterproof properties.
- Stratum spinosum
- Stratum basale (also called the )
- Stratum corneum: outer layer of the epidermis
“Come on, Let's Get Some Beers”: Corneum, Lucidum, Granulosum, Spinosum, and Basalis are the 5 layers of the epidermis.
- Basement membrane
- Hemidesmosomes: connect the epidermis to the basement membrane
- Collagen fibrils: connect stratum basale to the papillary layer
- Consists of fine, loosely arranged collagen fibers
- Supplies the epidermis with nutrients
- Plays an important role in temperature regulation
- Forms dermal ridges, which connect dermal papillae (extension of the papillary dermis into the epidermis) to epidermal downgrowths known as epidermal ridges or rete ridges
- Contains Meissner corpuscles (for fine-touch and two-point discrimination) and free nerve endings
- Contains immune cells (mast cells and macrophages)
- Consists of thick, densely packed fibers (e.g., reticular, elastic, and collagenous) that provide structure and support to the skin and its components
- Contains Ruffini corpuscles (mechanoreceptors): responsible for mechanical pressure and the sensation of distortion
- Contains sweat glands, sebaceous glands, and the roots of hair follicles
- Langer lines
Subcutis (also called hypodermis)
- Derived from mesoderm
- Consists mainly of subcutaneous fat that protects from cold and trauma
- Contains superficial veins and free nerve endings
- Contains Pacinian corpuscles (mechanoreceptors) that are responsible for the sensations of vibration and pressure
- Collagenous and elastic fibers in this area anchor the skin (epidermis, dermis) to the deep fascia.
- Allows for the subcutaneous administration of medication
Cells of the skin
Cells of the epidermis 
The epidermis is mainly composed of four different types of cells.
- Definition: principal cells of the epidermis
- Primarily protect against environmental damage and form a barrier against pathogens
- Protect against ultraviolet (UV) radiation by storing melanin produced by melanocytes
- Produce proinflammatory mediators to activate the immune system when exposed to pathogens
- Aid in the process of wound healing
- Form tight junctions with nerve endings and hold lymphocytes and Langerhans cells in place.
- Clinical significance
- Definition: -producing cells derived from neural crest cells
- Location: hair, iris and choroid of the eye, stratum basale of the skin
Function: melanin synthesis and storage
- Melanin is a dark pigment synthesized and stored in melanosomes (organelles within melanocytes).
- Dendritic processes transfer melanosomes to adjacent and distant keratinocytes.
- Melanocytes are stimulated by MSH, ACTH, and sunlight (UV-A): MSH and ACTH share the same precursor, proopiomelanocortin (POMC).
Synthetic pathway of melanin
- Phenylalanine → L-tyrosine
- L-tyrosine → L-3,4-dihydroxyphenylalanine (DOPA)
- DOPA → melanin (brown-black pigment)
- Clinical significance
- Definition: : macrophages of the skin; a type of dendritic cell
- Location: : stratum spinosum
- Clinical significance
- Definition: mechanoreceptors for deep static touch features (e.g., shapes, edges)
Skin appendage includes:
- Hair follicles
- Perionychium: epidermal tissue surrounding the root and base of the nail
- Eponychium: proximal layer of epidermis extending over the nail base
- Hyponychium: epidermal tissue immediately underlying the free distal edge of the nail
- Nail plate (nail body)
- Nail fold: depression proximal to the nail plate from which the nail grows
- Vascular supply
- Innervation: trifurcation of the dorsal volar digital nerve (supplying the nail fold, pulp, and distal tip of the finger)
- Definition: invaginations of the epidermis into the deep dermis, forming a cavity where the hair grows and develops
- Hair shaft
- Hair bulb
- Arrector pili muscle
|Sebaceous glands||Sweat glands|
|Eccrine sweat glands||Apocrine sweat glands|
|Location and distribution|| |
|Function|| || |
|Regulation of secretion|| |
The main functions of the skin include: 
- Barrier and protection against the external environment
- Thermoregulation (e.g., perspiration, regulation of blood circulation)
- Sensory function: sensations of pressure, vibration, touch, pain, and temperature
- Hormone synthesis of vitamin D
- Melanin synthesis: provides protection against ultraviolet (UV) radiation and determines the color of the skin and iris (see “Synthetic pathway of melanin” above)
Skin epithelium is derived from ectoderm.
- Signaling via the Wnt pathway prevents ectodermal progenitor cells from responding to fibroblastic growth factors (FGFs), which promotes a response to bone morphogenetic protein (BMP) signaling and, ultimately, leads to the differentiation into the embryonic epidermis.
- Lack of Wnt signaling causes the progenitor cells to respond to FGFs, which downregulates BMP signaling and promotes neurogenesis (i.e., differentiation into the neuroectoderm).
- Epidermal appendages (e.g., hair follicles, sweat glands) are formed from invaginations of the primitive epidermis into the dermis, with subsequent cell differentiation into the corresponding cell types (e.g., follicle cells, eccrine or apocrine sweat gland cells). 
- Dermis is derived from mesoderm.
- Melanocytes, Langerhans cells, and Merkel cells are derived from neural crest and migrate to the epidermis starting from the 12th week of embryonic development.