Key Concepts

Click here to see the image file.


The epidermis is derived primarily from ectoderm. Downward proliferations of epidermal cells differentiate to produce the epidermal appendages of hair, glands (apocrine, eccrine, and sebaceous) and nails. Cells from other germ layers do contribute to the final product.


The periderm is a superficial layer of cells which develops from the primordial single-cell-layered epidermis and forms a transient covering for the epidermis during much of the remainder of its development. Periderm is a unique feature of developing epidermis; no similar structure occurs in the development of other epithelia.

Stratification and Differentiation of the Developing Epidermis

Two developmental pathways are proceeding simultaneously in the early epidermis, stratification and differentiation. As new keratinocyte layers are formed (stratification), the cells within those layers are also acquiring new properties characteristic of their location within the epidermis (differentiation). In the fully developed epidermis, the stratification developmental pathway is turned off; the only operating developmental pathway is that of differentiation, that is, the coordinated spatial and temporal maturation of keratinocytes as they pass upwards through the epidermis to the cornified cell layer.

Non-Keratinocyte Cells of the Epidermis

Three cells essential for the function of the mature epidermis are not keratinocytes. Two of them are derived from extracutaneous sources and migrate from their tissue of origin into the epidermis. The third probably derives from the keratinocyte but is so extensively modified by differentiation that it bears no resemblance.


Melanocytes are pigment-producing dendritic cells in mature epidermis. They are derived from the neural crest and migrate into the epidermis in the 6th week of embryonic life. They are functionally immature during their migration.

Langerhans Cells

Langerhans cells are dendritic cells derived from the mesenchyme. They will be antigen processing and presentation cells in the mature epidermis. They are present in epidermis early in the 6th week of gestation.

Merkel Cells

Merkel cells arise from the keratinocyte lineage and develop into sensory receptors in the mature epidermis. They are the last of the nonkeratinocyte cells to appear in the epidermis. Merkel cells are part of the "diffuse neuroendocrine system" and contain the cytoplasmic "dense core granules" which characterize cells of this type. One of the more interesting hypotheses regarding their function is that they somehow direct the wiring of the dermis.

Epidermal Appendages

The Pilosebaceous Unit

The hair follicle and sebaceous gland develop together as a unit, the pilosebaceous unit, from a collaborative interaction between the epidermis and dermis. The result is a downward growth of keratinocytes into the dermis. Important parts of the hair follicle, the dermal papilla and the follicular sheath, are derived from the mesenchyme.

Canalization of the hair peg

The hair peg differentiates into matrix cells, which will ultimately form the hair shaft and inner root sheath and the new hair's supporting structure, the outer root sheath and the solid peg must become a hollow tube.

The follicle matrix forms from the longitudinally arranged interior cells and is spatially organized so that specific cells will give rise to the concentric layers of the inner root sheath and the hair shaft. This so-called hair cone actually differentiates into FIVE different concentric layers.

Follicular keratinization as defined by the presence of keratohyalin in the cells of the hair canal and by the presence of trichohyalin in the cells of the hair matrix occurs in week 16 of gestation.

Programmed cell death occurs above the hair cone, leading to the formation of a hollow tube or hair canal and the hair tract. Cells of the hair canal keratinize at the same time that the canal is formed. Although the hair canal is patent by about this time in development, the opening of the hair follicle is still closed and the follicle does not contain a hair.

Bulbous hair peg

The glands of the pilosebaceous unit differentiate from hair peg keratinocytes.

The hair peg becomes rounded (bulbous) at the dermal end and mostly encloses the cells of the dermal papilla.

The apocrine and sebaceous primordia, the attachment site for the arrector pili muscle, the hair canal, and the hair itself form simultaneously.

Three protrusions form along the shaft of the bulbous hair peg - one in each of the upper, middle, and lower portions of the hair peg. The uppermost usually involutes, but in certain locations it will differentiate into an apocrine gland; the middle bulge will differentiate into a sebaceous gland; the lowermost bulge will develop into the attachment site for the arrector pili muscle.

The growing hair advances up the hair canal and hair tract, pushing debris ahead of it until it finally erupts from the scalp.

Eccrine Glands

Eccrine glands develop from downward growths of basal keratinocytes which twist and aggregate into a glomerulus-like structure at the dermal subcutaneous boundary. Lumen formation occurs as the keratinocytes differentiate. In contrast to pilosebaceous unit development, which proceeds in a cephalocaudal direction, eccrine gland formation occurs first on the palms and soles, then the axillae, and lastly, the general body surface.

Apocrine Glands

The apocrine gland is the last of the epidermal glands to develop. The formation of the duct and and the gland itself follows the pattern of the eccrine gland in most details.

The Nail Unit

The dorsal ridge of the nail is the first structure in the epidermis to keratinize.

The nail-forming matrix epithelium arises from a wedge-shaped invasion of epidermis into what will become the proximal nail fold.

Dermal-Epidermal Junction

The dermal-epidermal junction (DEJ) appears very early in development and has all the characteristics of the adult structure by the 9th week of gestation.



The cells of the dermis are derived from somite mesoderm. Fibroblasts, which secrete the connective tissue matrix, Schwann cells, which will form the perineural structures, and endothelial cells, which form the blood vessels differentiate very early from the primordial dermal mesenchyme. Adipocytes, which form the fat lobules of the subcutaneous tissue arise later from the same source. Macrophages, pericytes, and mast cells appear last.

Organization and Matrix

The embryonic dermis consists of a syncytium of interconnected cells suspended in a watery matrix of hyaluronic acid. The cells differentiate into fibroblasts which replace the primordial dermis with a cell-poor dense fibrous matrix of collagen, elastin, and dermatan sulfate. The fibrillar components of the dermis continue to develop well after birth.

Vessels and Nerves

Vascular structures in the skin are formed in situ from endothelial cells which differentiate from primitive mesenchymal cells and aggregate into tubular structures. In contrast, the nerves grow into the developing skin, but the Schwann cells which will eventually associate with them are intrinsic to the primordial dermis. Nevertheless, the two arborizing systems develop in parallel.