DSF Skin Dev

Question 1

3 layers of skin

Answer 1

Epidermis, Dermis, Hypodermis

Epidermis separated from dermis by basement membrane zone: the dermal-epidermal junction

Question 2

What does epidermis develop from?

Answer 2

Surface ectoderm

Question 3

Collodion Baby

Answer 3

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

Question 4

Epidermis cell turnover

Answer 4

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

Question 5

Epidermolysis Bulbosa Simplex

Answer 5

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

Question 6

Epidermolytic Ichthyosis

Answer 6

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

Question 7

Keratinization

Answer 7

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

Question 8

Cornified envelope (CE)

Answer 8

Epidermal structure
Covalently cross-linked protein polymer that forms under plasma membrane
Mechanical reinforcement, hydration, cytokine-mediated initiation of inflammation, protection from UV damage

Question 9

Extracellular hydrophobic phase of epidermis

Answer 9

Made of specialized lipids synthesized by terminally differentiating keratinocytes
Involved in permeability, desquamation, antimicrobial peptide activity, toxin exclusion, selective chemical absorption

Question 10

Keratohyalin granules

Answer 10

Present in SG

Composed mostly of (pro)filaggrin, keratin filaments, loricrin

Question 11

Filaggrin

Answer 11

(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

Question 12

Loricrin

Answer 12

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

Question 13

Ichthyosis

Answer 13

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

Question 14

Ichthyosis Vulgaris

Answer 14

Mutation in FLG gene - abnormal filaggrin
AD inheritance
Onset: infancy/early childhood
Fine white scales - extensor surface of extremities, flexural sparing

Question 15

X-LR Ichthyosis

Answer 15

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

Question 16

Lamellar Ichthyosis

Answer 16

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

Question 17

Transglutaminase

Answer 17

Involved in keratinization of epidermis
Cross-links loricrin (after binds to desmosomal stuctures) to plasma membrane
Forms cornified cell envelope

Question 18

Harlequin Icthyosis

Answer 18

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

Question 19

Derivation of epidermal cells

Answer 19

Melanocytes - neural crest
Merkel cells - surface ectoderm
Langerhans cells - (monocytes) - mesoderm

Question 20

Albinism

Answer 20

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

Question 21

Oculocutaneous albinism (type IA)

Answer 21

Mutation in TYR gene; no Tyrosinase

Complete inability to synthesize melanin in skin, hair, eyes

Question 22

Piebaldism

Answer 22

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)

Question 23

Waardenburg Syndrome (type I)

Answer 23

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

Question 24

Dermal-Epidermal Junction

Answer 24

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

Question 25

Epidermolysis Bullosa

Answer 25

Dermal-Epidermal Junction dysfunction
Family of inherited genodermatoses characterized by blistering in response to minor trauma
Blister level categories: simplex, junctional, dystrophic subtypes
Cutaneous involvement varies from localized to widespread blistering
Extracutaneous involvement varies from none to severely debilitating/lethal
Dx made by immunofluorescent and/or EM followed by DNA analysis

Question 26

Junctional Epidermolysis Bullosa

Answer 26

Mutations in laminin beta3: cause blister formation w/in lamina lucida of the BMZ
From birth or early infancy, affected individuals have blistering over large regions of the body
Nails usually severely affected
Blistering also affects mucous membranes, such as moist lining of digestive and airway tracts
Extensive blistering leads to scarring and formation of granulation tissue - bleeds easily and profusely, making affected infants susceptible to serious infections

Question 27

Dystrophic Epidermolysis Bullosa

Answer 27

Defects in anchoring fibrils
Mutations of gene coding for type VII collagen, cause blisters that heal w/ scarring and milium formation
From birth/early infancy
Generalized blistering early, usually becomes localized to repetitively traumatized areas such as knees
These areas show a characteristic scarred, dystrophic appearance
Nail dystrophy/loss w/ atrophic scarring of distal digits common

Question 28

What is dermis mostly derived from?

Answer 28

Mesoderm
Trunk: ventral dermis derived from parietal layer of lateral plate mesoderm, dorsal dermis derived from dermatomal divisions of the somites

Question 29

Where is dermis of head and neck derived from?

Answer 29

Neural crest cells

Question 30

Where are skin appendages derived from?

Answer 30

Ectoderm

Question 31

Ectodysplasin (EDA)

Answer 31

Molecule related to TNF, plays a role in regulation of formation of ectodermal structures
Expressed in keratinocytes, outer root sheath of hair follicles, and sweat glands

Question 32

Hypohidrotic Ectodermal Dysplasia (HED)

Answer 32

Mutations in EDA or its receptor (EDAR)
Hair is absent/thin; nails, sweat and sebaceous glands are hypoplastic; skin is dry; teeth are absent/malformed/small
Can be life-threatening: children w/ HED are unable to sweat - susceptible to febrile seizures and hyperthermia during hot weather

Question 33

Label structures of hair anatomy

Answer 33

x

Question 34

4 phases of wound healing (skin)

Answer 34

1. Coagulation phase
2. Inflammatory phase
3. Proliferative and migratory phase - this is when epithelialization occurs
4. Remodeling phase

Question 35

Mesenchyme

Answer 35

Embryonic tissue w/ pluripotency, undifferentiated

Underlies ectoderm - forms Dermis