The document outlines the embryological development of the skin, detailing the formation of the epidermis, dermis, and skin appendages during various fetal stages. It describes the roles of different cell types such as melanocytes, Langerhans cells, and Merkel cells, and highlights the process of epidermal stratification and differentiation. Clinical relevance, including conditions like collodion baby and gene defects, is also discussed.

1. Embryology of the Skin
Presented by:
Alanoud Al-Marzoug
R2

2. Outline
Epidermal
Development
Development of
the specialized
cells of the
epidermis
Development
of the Dermis
and
Subcutis
Development
of the dermal-
epidermal
junction
Development
of the Skin
Appendages
 Melnocytes
 Langerhans cells
 Merckle cells
 Hair Follicle
 Sebaceous Gland
 Nails
 Sweat Glands
(APOCRINE, ECCRINE)

3. • During the 3rd
week after fertilization, the human embryo undergoes
gastrulation , that results in the formation of the three embryonic
germ layers :
• Ectoderm.
• Mesoderm.
• Endoderm.
INTRODUCTION

4. Embryonic Origin of Skin
Ectoderm Mesoderm
Surface Ectoderm Neuroectodermal fate
- Dermis of trunk and extremities
- Fibroblast
- Hypodermis; adipocytes
- Muscles
- Blood vessels
- Mast cells
- Langerhans cells
- Macrophages
- Keratinocytes
- Merkle cells
- Melanocytes
- Nerve and sensory
receptors
- The dermis of the
face and frontal
scalp.

5. 1
Specification
- Embryonic period
- (0 to 60 days)
 The ectoderm
 epidermis.
 mesodermal and
neural crest cells
 dermis.
2
Morphogenesis
- Early fetal period
- (2 to 5 months)
 formation of:
specialized structures,
epidermal stratification,
epidermal appendage,
subdivision between the
dermis and subcutis, and
vascular formation.
3
Differentiation
- Late fetal period
- (5 to 9 months)
 The newly specialized
tissues further develop
and assume their
mature forms.
Fetal skin development can be divided into three overlapping stages

6. Epidermal
Development
Development of
the specialized
cells of the
epidermis
Development
of the Dermis
and
Subcutis
Development
of the dermal-
epidermal
junction
Development
of the Skin
Appendages
 Melnocytes
 Langerhans cells
 Merckle cells
 Hair Follicle
 Sebaceous Gland
 Nails
 Sweat Glands
(APOCRINE, ECCRINE)

7. Epidermal Development
Surface Ectoderm
Basal
layer
Periderm
Intermediate
layer
Granular
layer
Cornified
layer

8. Epidermal Development
Surface Ectoderm
Basal
layer
Periderm
Intermediate
layer
Granular
layer
Cornified
layer
6 weeks
8 Weeks
K5 K14
K1 K10
22-24 weeks
24 -26 weeks
Head
Palms
Soles
*by the end of 2nd
trimester:
Periderm cells are sloughed off and form part
of the vernix caseosa (coats newborns)

9. Summary
• Epidermal Stratification: Formation of Epidermal layers. (P63 gene expression required)
• Terminal Differentiation: Formation of mature keratinizing epidermal cells.
6 weeks
8 weeks
15 weeks
22-24 weeks
24-26 weeks
24 weeks
End of third trimester
Full Barrier Function
Ectoderm consists of Basal layer and Periderm
Epidermal Stratification starts
Follicular keratinization
Cornification starts + inter-follicular epidermal keratinization
Full stratum Corneum
All layers of Keratinized epidermis identifiable (Complete
Epidermal Stratification).
Epidermis is similar to adult skin
Few weeks after birth (3 weeks).

10. Clinical Relevance
• Collodion Baby:
Encased in a Taut, shiny, transparent membrane that is formed by aberrant
stratum corneum .

11. • After shedding the Collodion membrane, most of these infant manifest with:
Lamellar Ichthyosis or Congenital Ichthyosiform Erythroderm
• Mood of inheritance?
• Gene defect?
• Clinical Presentation?
AR
TGM1 gene (transglutaminase deficiency) or ABCA12 (ATP binding cassette A12)
1- Collodion membrane at birth with underlying erythroderma → evolves to thick dark scales with flexural involvement.
2- Associated ectropion, eclabium, scarring alopecia PPK, heat intolerance (heat stroke),hypernatremia.

12. Epidermal
Development
Development of
the specialized
cells of the
epidermis
Development
of the Dermis
and
Subcutis
Development
of the dermal-
epidermal
junction
Development
of the Skin
Appendages
 Melnocytes
 Langerhans cells
 Merckle cells
 Hair Follicle
 Sebaceous Gland
 Nails
 Sweat Glands
(APOCRINE, ECCRINE)

13. All melanocytes are functional and in place at birth
 Unique Migration:
Trunk: dorsolaterally then ventrally around the trunk to ventral midline
Scalp and face: Anteriorly
Extremities: distally
Melanocytes
First Identified within the epidermis 2 months (50 days)
Melanin Production 4 months (Fitz 3 months)
Trasfer Melanosomes to Keratinocytes 6 months

14. Melanocytes
Dermal melanocytes:
• present throughout the dermis during embryonic development.
Eventually, most of them migrate to the epidermis or undergo
apoptosis.
• With the exception of certain anatomic sites (head and neck, dorsal
aspects of the distal extremites and presacral area), which correspond
to the most common locations for dermal melanocytoses and blue
nevi.

15. Clinical Relevance
• Mood of inheritance?
• Gene defect?
• Clinical Presentation?
White forelock (poliosis)
AD
C-kit gene mutation
White forelock (poliosis)
Irregularly-shaped leukoderma favoring
anterior trunk, extremities, forehead
(spares hands, feet, hips, shoulders),
otherwise healthy.
Piebaldism

16. Markers:
Langerhans cells
First Identified within the epidermis 6-7 weeks (40 days)
Fully developed 14 weeks
• CD45
• CD207 (Langrein)
• CD1a
• S100
• Vimentin
S100 expression
Eslamc +S100
Eccrine
Schwan
Langerhan
Adipocytes
Melanocytes
Chondrocytes

17. • Highly innervated neuroendocrine cells involved in mechanoreception.
• First identified in palmo-planter epidermis: 8-12 weeks EGA.
• Particularly dense over volar skin.
• Markers:
Merkel cells
 CK20
 Chromogranin
 Somatostatin
 Calcitonin
 Synaptophysin
 Vasoactive peptide
 Neuron-specific Enolase

18. Epidermal
Development
Development of
the specialized
cells of the
epidermis
Development
of the Dermis
and
Subcutis
Development
of the dermal-
epidermal
junction
Development
of the Skin
Appendages
 Melnocytes
 Langerhans cells
 Merckle cells
 Hair Follicle
 Sebaceous Gland
 Nails
 Sweat Glands
(APOCRINE, ECCRINE)

19. • The embryonic tissue that forms the dermis depends on the specific body site.
DERMIS
Dermis of the face and anterior scalp Neural crest ectoderm
Dermis of the back dermomyotome of the embryonic somite
Dermis of extremities and ventral trunk lateral plate mesoderm

20. DERMIS
• The ratio of collagen III to collagen I is 3:1 (the reverse of adult dermis).
• Dermal vasculature: by the end of the first trimester, but it undergoes extensive remodeling in
utero and is not fully mature until after birth.
• Nerve networks: by the mid to late first trimester, and they tend to follow the vascular pattern.
• Accumulation of subcutaneous fat begins during the second trimester and continues
through the third trimester, when distinct lobules separated by fibrous septae are
formed.
6–8 weeks Dermal fibroblasts
9 weeks Demarcation between dermis and underlying skeletal
condensations
12- 15 weeks Distinguish Papillary from reticular dermis
22 – 24 weeks Elastic fibers first detected

21. Clinical Relevance
Ehler Danlos Syndrome

22. Epidermal
Development
Development of
the specialized
cells of the
epidermis
Development
of the Dermis
and
Subcutis
Development
of the dermal-
epidermal
junction
Development
of the Skin
Appendages
 Melnocytes
 Langerhans cells
 Merckle cells
 Hair Follicle
 Sebaceous Gland
 Nails
 Sweat Glands
(APOCRINE, ECCRINE)

23. • As development progresses, the flat embryonic DEJ acquires the
rete ridges and dermal papillae that characterize the adult DEJ.
Dermal Epidermal Junction
8 weeks Skin specific components to the DEJ start to appear
(Laminin 1, Collagen 4, Heparin sulfate)
12 weeks Almost all structures of the mature DEJ are in place

24. Epidermal
Development
Development of
the specialized
cells of the
epidermis
Development
of the Dermis
and
Subcutis
Development
of the dermal-
epidermal
junction
Development
of the Skin
Appendages
 Melnocytes
 Langerhans cells
 Merckle cells
 Hair Follicle
 Sebaceous Gland
 Nails
 Sweat Glands
(APOCRINE, ECCRINE)

25. • Skin appendages (Hair, Nails and Sebaceous Glands ) have both
 Epidermal and dermal components that are critical in embryogenesis.
SKIN APPENDAGES

26. Hair Follicle Development
• Follicle formation is initiated by signals from the dermis that direct the embryonic
epidermis to form focal thickenings, called placodes.
• Placodes are first seen on the scalp and face
• They subsequently develop in a caudal and then in a ventral direction
• The epidermal placodes instruct the underlying dermal cells to condense and form
the presumptive dermal papilla.
• The dermal papilla then directs the keratinocytes of the placode to proliferate and
extend deeper into the dermis, thereby forming the hair germ.
• The base of the developing hair follicle surrounds the presumptive dermal papilla,
forming the hair peg.
First
dermal
signal

27. Hair Follicle Development
The superficial portion of the developing hair
follicle has two distinct bulges:
• Superficial bulge  sebaceous gland.
• Deeper bulge
 The insertion point of the future arrector pili
muscle
 The location of the presumptive follicular
stem cells

28. • The first hairs that appear, lanugo (downy hair) are fine, soft and lightly pigmented.
• Begins to appear by the end of 12th
week and is plentiful by the 17th
-20th
week.
• They help to hold the vernix caseosa on the skin.
• Lanugo is replaced during the perinatal period by coarser hair.
Hair Follicle Development

29. Hair Follicle Development
• Hair follicles undergo further
maturation during the
second trimester, forming
seven concentric cell layers.

30. Hair Follicle Development
10 – 11 weeks Placodes (first seen on scalp and face)
12 – 14 weeks Hair Peg
12 – 24 weeks 7 concentric hair follicle layers
19 – 21 weeks Hair canal fully formed (visible hair)
24 – 28 weeks The hairs continue to grow (anagen > catagen > telogen)
After birth The third hair cycle is initiated (asynchronous hair cycle)

31. • Sonic hedgehog (SHH):
a signaling molecule secreted by cells of the developing hair follicles, is required
for the maturation of the dermal papilla and for the progression of the follicle
placode to the hair bulb stage.
• SHH is also critical for the transition from the telogen to anagen during postnatal
hair cycling.
Hair Follicle Development

32. • First seen: 13–16 weeks GA as the most superficial bulge on the
developing hair follicle.
• Maternal hormones contribute to sebaceous gland hypertrophy and
increased synthesis and secretion of sebum during the second and
third trimesters. (start secretion intrauterine)
SEBACEOUS GLANDS

33. • Sweat glands are of two types:
1. Eccrine:
 located throughout most of the body.
 The ducts open into the skin surface.
 Begin to function shortly after birth (Do Not function intrauterine)
1. Apocrine:
 Confined to the axilla, areola, and pubic and perineal regions.
 Ducts open into the upper part of hair follicles superficial to the opening of the sebaceous glands.
 Function transiently during the 3rd
trimester and subsequently becomes quiescent in the neonate.
 Begin to function during puberty.
SWEAT GLANDS

34. SWEAT GLANDS
55 – 65 days Eccrine glands begin to develop on the volar surfaces of the hands
and feet, beginning as mesenchymal pads
12 -14 weeks parallel ectodermal ridges are induced which overlay these pads.
5th
Month • Dermatographics (fingerprints) seen on digit tips
• Interfollicular eccrine and apocrine glands begin to bud
7th
Month The cells of the apocrine glands become distinguishable
• Palmoplantar eccrine sweat gland start to develop during 1st trimester and fully
developed in 2nd trimester.
• Like sebaceous glands, apocrine glands typically arise from the upper portion of a
hair follicle, unlike to the inter-follicular eccrine gland which originate
independantly.

35. 9 weeks Nail apparatus developed from epidermis dorsal tip of the digit
12 weeks Primordial nail matrix
15 weeks Nail matrix completely developed
5 months Nail plate completely covering nail bed
NAILS

36. Quiz

37. The embryonic periderm becomes part of the?
a. Vernix caseosa
b. stratum corneum
c. stratum basale
d. dermis
e. hair follicle

38. Embryologically, epidermal stratification begins at
approximately what estimated gestational age?
a. 4 weeks
b. 8 weeks
c. 12 weeks
d. 16 weeks
e. 20 weeks

39. Keratinocytes are derived from which of the following?
a. Endoderm
b. Mesoderm
c. Ectoderm
d. Neural Crest
e. Bone marrow precursors

40. • Dermatology by Bolognia J. 4th
Ed.
• Fitzpatrick’s dermatology in general medicine. 8th
Ed.
References: