DSF Skin Dev Flashcards
3 layers of skin
Epidermis, Dermis, Hypodermis
Epidermis separated from dermis by basement membrane zone: the dermal-epidermal junction
What does epidermis develop from?
Surface ectoderm
Collodion Baby
Cells of the periderm are gradually sloughed into the amniotic fluid, normally completed by the 21st week
Peridermal cells form part of the protective vernix caseosa (a greasy deposit covering the skin of a baby at birth)
In some fetuses peridermal cells persist much longer after birth, forming a “shell” or “cocoon” around the newborn infant
Epidermis cell turnover
Normal transit time for basal cell (from time loses contact w/ basal layer to time enters SC) is at least 14 days
Transit through SC and subsequent desquamation require another 14 days
Epidermolysis Bulbosa Simplex
Abnormality in primary keratin
Mutations in genes KRT5 and KRT14, specifically expressed in stratum germinativum
Common subtypes present at birth
Skin exceptionally fragile and blisters
Blistering primarily affects hands and feet, usually heal w/o scars
Often shows nail involvement
Epidermolytic Ichthyosis
Abnormality in secondary keratin
Mutations in KRT1 or KRT10 (specifically expressed in stratum spinosum) associated w/ blistering in the suprabasal layers
At birth baby’s skin seems to be fragile and may show blistering, w/o much scaling
During 1st couple years, blistering tendency reduces but widespread redness, scaling, thickening of skin becomes more obvious - often linearly arrayed in flexural creases: “corrugated cardboard”-like scaling
Skin infections common
Keratinization
Keratinocyte differentiation; genetically programmed, carefully regulated complex series of morphologic changes and metabolic events whose endpoint is a terminally differentiated, dead keratinocyte (corneocyte) that contains keratin filaments, matrix protein, and a protein-reinforced plasma membrane w/ surface-associated lipids
Cornified envelope (CE)
Epidermal structure
Covalently cross-linked protein polymer that forms under plasma membrane
Mechanical reinforcement, hydration, cytokine-mediated initiation of inflammation, protection from UV damage
Extracellular hydrophobic phase of epidermis
Made of specialized lipids synthesized by terminally differentiating keratinocytes
Involved in permeability, desquamation, antimicrobial peptide activity, toxin exclusion, selective chemical absorption
Keratohyalin granules
Present in SG
Composed mostly of (pro)filaggrin, keratin filaments, loricrin
Filaggrin
(from profilaggrin)
Component of keratohyalin granule present in SG
Filaggrin aggregates w/ keratin to form macrofilaments, then is degraded into molecules that contribute to hydration of SC and help filter UV radiation
Loricrin
Component of keratohyalin granule present in SG
Major protein component of CE
Upon release from keratohyalin granules, loricrin binds to desmosomal structures and is subsequently cross-linked to plasma membrane by tissue transglutaminases (TGMs) to form CE
Ichthyosis
Abnormal keratinization
disorders resulting in non-inflammatory scaling, dryness, cracks in skin that may form deep fissures
Most types inherited, and usually present at birth/early years
Ichthyosis Vulgaris
Mutation in FLG gene - abnormal filaggrin
AD inheritance
Onset: infancy/early childhood
Fine white scales - extensor surface of extremities, flexural sparing
X-LR Ichthyosis
Abnormal Steroid Sulfatase
Exclusively affects males
Onset at birth
Mutation in gene coding for steroid sulfatase: which catalyzes the hydrolysis of cholesterol sulfate, important process in normal desquamation
Affects keratinization at stratum granulosum
Initially resembles IV, scaling turns darker w/ increasing age; affects posterior neck, upper trunk, and extensor surfaces of extremities; cryptorchidism; corneal opacity
Lamellar Ichthyosis
AR inheritance
Onset at birth, mostly born as collodion babies
Brown, coarse scales, at times large; involve entire body
Mutation in TGM I gene - encodes for transglutaminase I
Transglutaminase
Involved in keratinization of epidermis
Cross-links loricrin (after binds to desmosomal stuctures) to plasma membrane
Forms cornified cell envelope
Harlequin Icthyosis
AR - most severe
Often stillborn
Prevents formation of cornified envelope
Mutation in ABCA12 gene: encodes for ATP-binding cassette transporter (lipid transporter) involved in lamellar granule secretion and epidermal lipid transport; normal lamellar granules are not found; no evidence of lipid lamellae that form b/w granular and cornified cells
Often premature and born w/ massive, shiny plates of SC separated by deep, red fissures that tend to form geometric patterns
Derivation of epidermal cells
Melanocytes - neural crest
Merkel cells - surface ectoderm
Langerhans cells - (monocytes) - mesoderm
Albinism
Results from dysfunction of a normal complement of pigment cells, which results from either enzymatic defects in biosynthesis of melanin, from melanosomal defects that interfere w/ melanin formatin, or from problems in intracellular transport and localization of proteins essential for melanin biosynthesis
Ocular nystagmus and reduced visual acuity, due to misrouting of optic nerve at optic hciasm and foveal hypoplasia = important features of albinism
Oculocutaneous albinism (type IA)
Mutation in TYR gene; no Tyrosinase
Complete inability to synthesize melanin in skin, hair, eyes
Piebaldism
AD inheritance
Mutation in c-KIT proto-oncogene: encodes for a cell surface transmembrane receptor tyrosine kinase; the kit gene is related to melanoblast migration, proliferation, differentiation, and survival
Lack of melanin in isolated patches
~90% affected individuals have a white section of hair near their front hairline (white forelock)
Waardenburg Syndrome (type I)
AD inheritance
Mutation in PAX3 gene, responsible for:
1. Expression of melanocyte survival genes
2. development of neural crest derivatives that contribute to bony and cartilaginous structures of the face
3. Migration and survival of melanoblasts in stria vascularis in cochlear wall
Pigmentation abnormalities associated w/ craniofacial abnormalities:
1. Poliosis (presence of white forelock)
2. Dystopia canthorum (lateral displacement of the medial canthi of the eyes) hallmark
3. Sensorineural defects
Dermal-Epidermal Junction
Basement membrane zone (BMX) that forms the interface b/w epidermis and dermis - provide resistance against external shearing forces
Supports, determines polarity of growth, directs organization of cytoskeleton in basal cells, provides developmental signals, semi-permeable barrier
3 networks:
1. Hemidesmosome-anchoring filament complex
2. basement membrane
3. anchoring fibrils
