Origin of Epidermal Cells

Origin of Epidermal Cells

• Presumptive epidermis forms after neurulation, initially one cell layer thick.
• It soon becomes two-layered in most vertebrates.
• The outer layer is a temporary covering called the periderm, is shed when the inner layer forms the true epidermis.
• The inner layer, or basal layer (stratum germinativum), is a germinal epithelium.
• The basal layer produces the spinous layer, and both epidermal layers are known as the Malpighian layer.
• The cells of the Malpighian layer divide to produce cells of the granular layer of the epidermis, whose cells contain granules of the protein keratin.
• Granular layer cells, unlike Malpighian layer cells, stop dividing and start differentiating into keratinocytes.
• As keratinocytes age and migrate outward, the keratin granules become more prominent and form cells of the cornified layer (stratum corneum).
• Cells of the cornified layer become flattened sacs of keratin protein with nuclei pushed to one edge.
• The cornified layer varies in depth, usually 10-30 cells thick.
• Outer cells of the cornified layer are shed shortly after birth, replaced by new cells from the granular layer.
• Throughout life, dead keratinized cells of the cornified layer shed at a rate of about 1.5 grams per day in humans.
• The mitotic cells of the Malpighian layer are the source of the new cells.
• Melanocytes from the neural crest reside in the Malpighian layer, where they transfer pigment sacs (melanosomes) to developing keratinocytes.
• Epidermal stem cells of the Malpighian layer bind to the basal lamina via integrin proteins.
• Cells down-regulate and lose integrins as they commit to differentiate and migrate into the spinous layer.

Growth Factors and Epidermal Development

• Transforming growth factor-α (TGF-α) stimulates epidermal development.
• TGF-α is an autocrine growth factor made by basal cells to stimulate their own division.
• Dysregulation of autocrine growth factors can lead to rapid cell production.
• An adult skin cell takes roughly 8 weeks to reach the cornified layer and remains there for about 2 weeks.
• In psoriasis, cells spend only 2 days in the cornified layer, resulting in excessive exfoliation.
• Psoriasis has been linked to TGF-α overexpression, secondary to inflammation.
• Transgenic mice with the TGF-α gene linked to a keratin 14 promoter develop scaly skin, stunted hair growth, and excess keratinized epidermis.
• Keratinocyte growth factor (KGF; fibroblast growth factor 7) is another growth factor needed for epidermal production.
• KGF is a paracrine factor produced by fibroblasts of the dermis.
• It is received by the basal cells of the epidermis, thought to regulate their proliferation.
• Transgenic mice with KGF made autocrine develop a thickened epidermis, baggy skin, too many basal cells, and no hair follicles.
• In transgenic mice, basal cells are forced into the epidermal pathway of differentiation instead of generating hair follicles.

Cutaneous Appendages

• Epidermis and dermis interact to create sweat glands and cutaneous appendages (hairs, scales, or feathers).
• The first sign of hair follicle primordium (hair germ) formation is an aggregation of cells in the epidermis basal layer.
• This aggregation is directed by underlying dermal fibroblast cells.
• Dermal signals likely cause stabilization of β-catenin in the ectoderm.
• Basal cells elongate, divide, and sink into the dermis.
• Dermal fibroblasts form a dermal papilla beneath the hair germ in response.
• The dermal papilla stimulates basal stem cells to divide more rapidly.
• Basal cells produce postmitotic cells that differentiate into the keratinized hair shaft.
• Melanoblasts differentiate into melanocytes and transfer pigment to the hair shaft.
• Two epithelial swellings grow on the side of the hair germ.
• The lower swelling cells may retain stem cells that regenerate the hair shaft when shed.
• The cells of the upper bulge form the sebaceous glands, which produce sebum.
• Sebum mixes with shed peridermal cells to form the vernix caseosa around the fetus at birth in many mammals, including humans.
• Pluripotent epidermal stem cells can become epidermis, sebaceous gland, or hair shaft cells.

Hair Types

• Lanugo is the first type of hair in the human embryo, thin and closely spaced.
• Lanugo is usually shed before birth and replaced by vellus.
• Vellus is short and silky and remains on areas usually considered hairless.
• Vellus can give way to terminal hair in some areas.
• Follicles that produced vellus can later form terminal hair and revert to vellus production.
• Armpit follicles produce vellus until adolescence, then produce terminal shafts.
• In normal masculine pattern baldness, scalp follicles revert to producing unpigmented vellus hair.

Patterning of Cutaneous Appendages

• Cutaneous appendages do not grow randomly over the body.
• Spaces between appendages (e.g., on the scalp) are similar from region to region.
• A reaction-diffusion process may be responsible for this pattern.
• Sonic hedgehog is the activator, a paracrine factor that acts locally without much diffusion.
• BMP4 or BMP2 is believed to be the inhibitor, both paracrine factors with a greater range of diffusion.
• BMPs may prevent dermal fibroblasts from aggregating.
• Sonic hedgehog may support the formation and retention of the dermal papilla.