Structure and function of skin

Which gene family encodes information for skin embryologic development

Homebox (Hox) genes

How does the embryonic skin develop?

Single layer of ectodermal cells and dermis of mesenchyme, ectoderm develops into stratum germinatum (basal cell layer) and stratum periderm (outer layer), then third layer (stratum intermedium), then adult like structure

Which part of the embryonic structures give rise to hair follicles, sebaceous glands, and apocrine sweat glands?

Stratum germinativum differentiates into hair germs

What is epidermal placode? What does it make?

Hair germs crowding in the basal layer of epidermis becoming buses, forms hair shaft, outer and inner root sheaths

What are morphogens? Name six

Substances controlling hair follicles development

1) Hox

2) Fibroblast growth factor

3) Transforming growth factor (TGF-b)

4) Sonic hedgehog

5) Wingless

6) Neurotrophins

What are the four phases of hair cycle?

Anagen (growth)

Catagen (regression)

Telogen (rest)

Exogen (shedding)

What is the predominant determinant of hair growth?

Photoperiod > ambient temperature

Why does telogen effluvium occur?

Severe illness or systemic stress can cause many hair follicles to enter synchronously into telogen and can shed

Which cells are primary targets that respond to hormones and mediate growth stimulating signals to follicular epithelium?

Dermal papilla cells (mesenchymal component of hair bulb)

What causes follicular atrophy vs. follicular dysplasia

Atrophy by alteration in factor controlling hair cycle like hormones, dystrophy by alteration in factors controlling hair structure like morphogens

What are two types of pigment and their colors?

Eumelanin is black/brown and pheomelanin is yellow/red

Which gene leads to production of the two types of melanins and how?

Activation of melanocortin 1 receptors (MC1R) leads to eumelanin, inhibition leads to pheomelanin

Which gene controls the shade of eumelanin?

Tyrosinase related protein 1 gene (TYRP1)

What is the name of the pattern assumed by nevoid and acquired skin diseases?

Blaschko lines

What are the four cell types within the epidermis and the %?

Keratinocytes 85%, melanocytes 5%, Langerhan’s cells 3-8%, Merkel cells 2%

What are the layers of the epidermis?

Stratum basale, stratum spinosum, stratum granulosum, stratum lucidum, stratum corneum

What are rete ridges and where are they normally found?

Projections of the epidermis into the dermis; normal in footpads, nasal planum, and lightly haired scrotum

What are the functions of basal keratinocytes?

Anchoring the epidermis to the dermis and stem cells (proliferation and reparation)

Which keratin filaments are present in stratum basale and what do they do

K5 and K14 attaches to neighboring cells through desmosomes and BMZ at hemidesmosomes

What are desmosomes?

Cell adhesion junction of epithelial tissues anchoring intermediate filaments and adjacent cells

What are 3 major gene families of desmosomal molecular components

Plakins (desmoplakin), armadillo proteins (plakoglobin, plakophillin), desmosomal cadherins (desmogleins, desmocollins)

What are hemidesmosomes and their major role?

Junctional complex along inner basal keratinocytes role is epidermal-dermal adhesion

Which components are targets that produce epidermolysis bullosa, pemphigoid, and bullous SLE?

Hemidesmosomes anchoring filament components

What are integrins

Surface adhesive receptors important in cell-cell and cell-matrix interactions

Which keratin filaments are present in the spinous layer?

K1/K10

What do the keratinocytes in stratum spinosum do?

Synthesize lamellar granules with glycoproteins, glycolipids, phospholipids, sterols, etc. that get secreted into granulosum

Which layer of the epidermis synthesizes keratohyaline granules?

Stratum granulosum

What is the composition of keratohyaline granules

Profilaggrin, keratin filaments, Loricrin

What is loricrin?

Cystine rich protein in keratohyaline granules that binds keratin filaments together in corneocyte and anchor them to cross-linked envelope

Where is the stratum lucidum found?

Footpads and nasal planum

What is the role of the cornfield envelope?

Structural support to the cell and provides a barrier to microorganisms and environmental harm

What is the role of involucrin?

Binds ceramides covalently and forms a backbone for attachment of intracellular lipids

What is the role of keratinocyte and epidermal transglutaminases?

Mediates sequential cross-linking of cornfield cell envelope precursor proteins

Where are transglutaminases expressed?

Stratum granulosum and upper stratum spinosum

What is keratin?

Highly stable disulfide bond-containing fibrous protein

What is prekeratin and where is it made

Fibrous protein synthesized in keratinocytes of stratum basale and spinosum, precursor

What are 4 steps of cornification

1) Keratinization (synthesis of principal fibrous proteins of the keratinocyte)

2) Keratohyaline synthesis (including filaggrin)

3) Formation of cross-linked insoluble stratum corneum cornified cell envelope (including involucrin)

4) Generation of neutral lipid-enriched intercellular domains from secretion of distinctive lamellar granules

What are the contents of lamellar granules?

Phospholipid, ceramides, FFAs, hydrolytic enzymes, sterols

What is the most important lipid component for lamellar arrangement in the stratum corneum and barrier function

Ceramides (amide-linked fatty acids with long chain amino alcohol sphingoid base)

Why are polyunsaturated fatty acids important?

Incorporated into ceramides, ceramides bind involucrin/proteins of CE and form a scaffold for the other lipids to bind

Also a precursor of eicosanoids