Skin development

Question 1

The epidermis and epidermal derivatives originate from what embryonic tissue?

Answer 1

Ectoderm

Question 2

The dermis is derived from what embryonic tissue?

Answer 2

**Mesenchyme of regional origin

• head -> neural crest and head mesoderm
• trunk and limbs -> somatic mesoderm
• back -> dermatome (part of a somite)

Question 3

What is the origin of melanocytes?

Answer 3

Neural crest

Question 4

What is the origin of Langerhans cells? What do they become?

Answer 4

Bone marrow… they later become APCs

Question 5

What is the origin of merkel cells?

Answer 5

Epidermal stem cells (in the basal layer)

Question 6

Where do melanocytes, langerhans cells, and merkel cells reside?

Answer 6

In the epidermis

Question 7

During development, what signaling is essential?

Answer 7

Ectoderm-mesenchyme cross signaling

Question 8

What protects the skin from amniotic fluid?

Answer 8

The vernix caseosa (formed by squames of periderm, hair and a white paste-like substance secreted by sebaceous glands)

Question 9

Hair follicles, sweat glands, and nails are derived form what?

Answer 9

Epidermal buds that extend into the forming dermis

Question 10

Describe epidermal development

Answer 10

• initially a single layer of cuboidal cells
• weeks 4-8= primitive 2 layer epidermis (peridermal cells)
• weeks 11-12= 3 layer epidermis (periderm, intermediate, and germinative/basal) **peridermal sloughing
• months 4-6 epidermis becomes multi-layered/mature (cornified, granulosum, spinosum, basale)

Question 11

What is the major function of the periderm in development?

Answer 11

Between weeks 12 and 18 the periderm is the major source of amniotic fluid via globular elevations containing microvilli

**globular projections pinch off after week 20, and the flat squames of periderm protect the underlying epidermis from the changing composition of amniotic fluid

Question 12

When do blood vessels appear in the papillae?

Answer 12

4th-5th week to supply the epidermis… These vessels become dense and also provide thermal control for the skin

Question 13

When does hair formation begin?

Answer 13

About week 9-12, but becomes more obvious around week 20 (thin lanugo/downy hair; helps hold the vernix caseosa next to the skin)

Question 14

What cells migrate into the epidermis early in embryonic development?

Answer 14

Melanocytes and Langerhans cells

Question 15

What is piebaldism?

Answer 15

• autosomal dominant
• mutation of the KIT proto-oncogene resulting in impaired migration of melanocytes

Question 16

What are the clinical symptoms of piebaldism?

Answer 16

• depigmented patches (congenital, recall vitiligo=acquired) often with speckles within
• stable, nonprogressive
• white forelock typical

Question 17

What is Waardenburg syndrome?

Answer 17

• rare genetic disease
• multiple genes implicated; result in abnormal development of melanocytes (NOT a migration problem like piebaldism)

Question 18

What are the clinical symptoms of Waardenburg syndrome?

Answer 18

**Cannot distinguish from piebaldism just based off skin symptoms, look for:

• deafness
• heterochromia irides (eyes are 2 colors)
• dystopia canthorum (wide distance between eyes)

Question 19

What structures are associated with the hair shaft?

Answer 19

• Sebaceous Gland (begins forming about one month after the hair follicle forms)
  
  • From “upper bud”
• Bulge that contains stem cells that can regenerate a hair bud, and interestingly, can transform into neural crest stem cells
  • From “deeper bud”
• Arrector Pili Muscle attaches to the dermal root sheath and the papillary layer of the dermis
• Melanoblasts associate with the cells of the hair bulb where they differentiate into melanocytes which transfer their melanosomes into the cells forming the hair

Question 20

What is a port wine stain?

Answer 20

Also called “Capillary malformation”

• Malformed, ectatic, dilated capillary to venule sized blood vessels
• Always present at birth (occurs in 0.3-0.6% of newborns)
• Tend to darken and thicken slightly over time

**Extends across face V1/V2/V3 distribution

Question 21

What is Sturge-Weber syndrome?

Answer 21

• most commonly associated with capillary malformations (port wine stains) in the V1 dermatome
• neurological findings (seizures, dev delay, migraines)
• ocular findings (congenital glaucoma, increased choroidal vascularity/tomato ketchup spot)

Question 22

What is an infantile hemangioma?

Answer 22

• “strawberry spot” **dynamic lesions
• most common vascular tumor (4-5%)
• composed of proliferating endothelial like cells that become clinically visible within the first months of life
  
  • at birth= white flat patch with fine pink/red vessels
  • 1-2 weeks proliferation begins
  • growth phase variable; 3-9 months (slowly involute)

Question 23

What is PHACE syndrome?

Answer 23

• Posterior fossa abnormalities (cerebellar problems)
• Hemangioma (segmental)
• Arterial anomalies
• Cardiac anomalies
• Eye anomalies
• Sternal clefting/supraumbilical raphe

Question 24

Describe hair follicle formation

Answer 24

• Hairs begin as Placodes/Buds within the germinative layer induced by signals from the dermis
• Cells from the placode proliferate and invaginate into the underlying mesenchyme forming a Hair Bud/Peg
• Hair bud becomes hair bulb and dermal papilla (formed under the influence of Shh from the bud from adjacent mesenchyme condensing) invaginate into its base

Question 25

Contrast eccrine and apocrine glands

Answer 25

\*\*The two types of sweat glands: * Eccrine= merocrine secretion (open to the surface of the skin) * Apocrine= apocrine secretion; cytoplasm released along with secretions (open near the sebatious gland)

Question 26

Describe nail formation

Answer 26

* precursors of nails are _thickenings of the surface ectoderm_ at the distal end of the digits (called Primary Nail Fields) * ten weeks for the fingers and 14 weeks for the toes * compressed plate of keratinocytes grows distally forming the _Nail Plate_ (Initially this is covered by a thin layer, the _Eponychium_ that later degenerates except at the nail base) * layer of skin beneath the free edge of the nail is called the _Hyponychium_ * nail growth reaches the tip of the finger by the eighth month and the toe tip by birth

Question 27

What is ectodermal dysplasia?

Answer 27

\*\*Over 150 rare syndromes * alterations in 2 or more of the structures that derive from the embryonic ectoderm * hair, teeth, nails, sweat glands, eye lens

Question 28

What is hypohidrotic ectodermal dysplasia (HED)?

Answer 28

* most often an x linked recessive condition * most common form of ectodermal dysplasia encountered by clinicians * ectodysplasin signaling pathway abnormality * EDA-A1 (extodysplasin A1), EDAR (Eda-A1 receptor), or EDARADD (EDAR associated death domain)

Question 29

What are the clinical symptoms of hypohidrotic ectodermal dysplasia (HED)?

Answer 29

* square forehead with frontal bossing * flattened nasal bridge * low lying ears * skin= thin and dry * sparse hair * hypo-anodontia/peg teeth * decreased ability to sweat \*\*avoid overheating