Integumentary System

Introduction

The skin provides a barrier between ourselves and our environment, it also contains specializations in different regions including hair, nails, glands and sensory receptors.

The two major tissue organizations of epithelial (ectoderm, epidermis) and mesenchyme (mesoderm connective tissue, dermis and hypodermis) are shown within skin. In addition, we have aslo extensive populating by melanocytes (neural crest) and sensory nerve endings.

It remains today as possibly the first epithelial specialization from which arose other epithelial specializations now located inside the body. The external skin specializations have many different roles and functions. This system is also an excellent model for distribution or "pattern" that is of interest.

Textbooks

Human Embryology Larson Chapter 14 p443-455
The Developing Human: Clinically Oriented Embryology (6th ed.) Moore and Persaud Chapter 20: P513-529

Objectives

Understand the embryonic origin and differentiation of the epidermis and dermis.
Understand the formation of hair and nails.
Understand the formation of sweat glands, mammary glands.
Understand the formation of teeth.
Brief understanding of associated abnormalities.

Skin Origins

Ectoderm forms the surface epidermis and the associated glands.
Mesoderm forms the underlying connective tissue of dermis and hypodermis.
Neural crest cells also migrate into the forming epidermis and the skin is also populated by specialized sensory endings.

Development Overview

Ectoderm and Mesoderm Origin

4 weeks

simple ectoderm epithelium over mesenchyme.

1-3 months

ectoderm- germinative (basal) cell repeated division of generates stratified epithelium.
mesoderm- differentiates into connective tissue and blood vessels.

4 months

basal cell- proliferation generates folds in basement membrane.
neural crest cells- (melanocytes) migrate into epithelium. These are the pigment cell of the skin.
embryonic connective tissue- differentiates into dermis, a loose ct layer over a dense ct layer. Beneath the dense ct layer is another loose ct layer that will form the subcutaneous layer.
Ectoderm contributes to nails, hair follictles and glands.
Nails form as thickening of ectoderm epidermis at the tips of fingers and toes. These form germinative cells of nail field.
Cords of these cells extend into mesoderm forming epithelial columns. These form hair follocles, sebaceous and sweat glands.

5 months

Hair growth initiated at base of cord, lateral outgrowths form associated sebaceous glands.
Other cords elongate and coil to form sweat glands.
Cords in mammary region branch as they elongate to form mammary glands. These glands will complete development in females at puberty. Functional maturity only occurs in late pregnancy.

Development of Skin

Skin is our largest organ, providing a protective layer between us and our environment

epidermis - surface ectoderm
dermis - mesoderm
ectoderm/msoderm interaction an inductive manner
epithelia/mesenchyme (last weeks lecture on kidney)

Regional Specializations

skin has different structures associated with different regions of the body
nails, hail, glands, teeth, eyelashes, eyebrow
2 main types of histological skin - thin (most of body) thick (soles of feet and hands)
- not the thickest skin

Epidermis

initially periderm
keratinization and desquamification
replaced by basal cells

Epidermis

week 4-5 early skin is a single ectodermal layer, stratum germinativum basal layer
week 11 forms intermediate layer
periderm then lost replaced by stratum corneum, keratinization and desquamification
week 10 epidermial ridges are formed by proliferation

Neural crest cells

Neural crest cells migrate into skin (late embryonic) form melanoblasts
day 40-50 differentiate into then melanocytes - form pigment granules
different content of melanin (Greek, melas = "black") accounts for differet skin colour

Dermis

lateral plate mesodermal in origin
forms connective tissue
afferent nerves influence dermal ridge formation

Blood Vessels

lateral plate mesodermal in origin
week 5 blood vessels form in mesenchyme
for capillary beds, extensive remodelling with development

Skin Dermatomes

pattern of skin innervation
area supplied by single spinal nerve
motor and sensory DRG
cutaneous nerve area

Keratin

large family of intermediate filament protein, 17+ isoforms
skin disease associated with mutations in keratin genes

Keratins are the major structural proteins of the vertebrate epidermis and its appendages, constituting up to 85% of a fully differentiated keratinocyte. Together with actin microfilaments and microtubules, keratin filaments make up the cytoskeletons of vertebrate epithelial cells. Traced as far back in the evolutionary kingdom as mollusks, keratins belong to the superfamily of intermediate filament (IF) proteins that form alpha-helical coiled-coil dimers which associate laterally and end-to-end to form 10-nm diameter filaments. The evolutionary transition between organisms bearing an exoskeleton and those with an endoskeleton seemed to cause considerable change in keratin. Keratins expanded from a single gene to a multigene family. Of the approximately 60 IF genes in the human genome, half encode keratins, and at least 18 of these are expressed in skin. Vertebrate keratins are subdivided into two sequence types (I and II) that are typically coexpressed as specific pairs with complex expression patterns. The filament-forming capacity of a pair is dependent upon its intrinsic ability to self-assemble into coiled-coil heterodimers, a feature not required of the invertebrate keratins (Weber et al 1988). Approximately 20,000 heterodimers of type I and type II keratins assemble into an IF. Mutations that perturb keratin filament assembly in vitro can cause blistering human skin disorders in vivo. (from Review Article)

Development of Glands

2 main types - sebaceous and sweat
both ectodermal in origin
form as ingrowth of ectoderm into the mesoderm

Sebaceous

associated with hair development
except plans penis and labia minora
these glands secrete vernix

Sweat Glands

mostly eccrine some apocrine
apocrine in axilla, pubic and nipple regions
- see also mammary gland development

Vernix Caseosa

(Latin, vernix caseosa = varnish)
covers fetal skin- secretion from sebaceous glands
protects skin from extraembryonic fluids amnion, urine
slippery and helps with parturition

Hair Development

week 9 -12
follicle forms in st. germinativum of epidermis
hair bud -> hair bulb
hair bulb forms hair
mesenchyme forms hair papilla
germinal matrix cells become keratinized to form hair shaft
arrector pili muscle develop in mesenchyme
week 12 - lanugo hair (L. lana = wool)
- first hair formed replaced postnatally
- bind vernix to skin
Melanocytes (neural crest) produce melanin which influences hair colour

Postnatal Development

puberty - coarse hair in pubis and axilla
- males face, chest, etc

Molecular Hair Development

EGF inhibits hair follicle formation
SHH Knockout mice
- Hair germs comprising epidermal placodes and associated dermal condensates were detected in both control and Shh -/- embryos, but progression through subsequent stages of follicle development was blocked in mutant skin. The expression of Gli1 and Ptc1 was reduced in Shh -/- dermal condensates and they failed to evolve into hair follicle papillae, suggesting that the adjacent mesenchyme is a critical target for placode-derived Shh. Despite the profound inhibition of hair follicle morphogenesis, late-stage follicle differentiation markers were detected in Shh -/- skin grafts, as well as cultured vibrissa explants treated with cyclopamine to block Shh signaling. Our findings reveal an essential role for Shh during hair follicle morphogenesis, where it is required for normal advancement beyond the hair germ stage of development. Chin etal Developmental Biology, v 205, n 1, Jan 1999, p 1-9

Molecular Hair Development

inappropriate activation of the Shh signal
shh transduction cascade in human epidermis can cause basal cell carcinoma. Here we show that during normal development of avian skin, Shh is first expressed only after the responsiveness to this protein has been suppressed in most of the surrounding ectodermal cells. Forced expression of Shh in avian skin prior to this time causes a disorganized ectodermal proliferation. However, as skin begins to differentiate, the forced expression of Shh causes feather bud formation. Subsequently, expression of Shh in interfollicular epidermis has little or no morphological effect. Restricted responsiveness to Shh in developing skin has functional consequences for morphogenesis and may have important implications for cutaneous pathologies as well
- - - Morgan etal. Developmental Biology, v 201, n 1, September 1, 1998, p1-12

Nail Development

week 10 fingernails before toenaois
as in limb development
nail field
- appears at tip and migrates to dorsal surface
thickened epidermis
surrounding cells form nail fold
keratinization of proximal nail fold forms nail plate
nails reach tip
- week 32 fingernails
- week 36 toenails
nail growth indicator of prematurity

Mammary Glands

week 6 epidermis downgrowth into dermis
modified sweat glands
- epithelia/mesenchyme inductive interaction
- mesenchyme forms connective tissue and fat
- mammary ridges- mammary bud formation
- pair of ventral regions axilla to inguinal
- pectoral regions generate breasts
- buds branch to form lactiferous ducts
- placental sex hormone
- only main duct formed at birth
Mammary Glands
- mammary pit
- forms fetal period
- depressed region at gland
- areola
- proliferation of connective tissue postnatally
- prior to puberty male and female glands the same
Mammary Glands-Puberty
- sex hormone estrogen stimulate growth
- full development approx 20 years
- mainly fat and connective tissue deposition
- growth also influenced by other hormones
- progereterone, prolactin, corticoids, growth hormone

Breast cancer

In 1994, two breast cancer susceptibility genes were identified: BRCA1 on chromosome 17 BRCA2 on chromosome 13
When an individual carries a mutation in either BRCA1 or BRCA2, they are at an increased risk of being diagnosed with breast or ovarian cancer at some point in their lives. Normal function of these genes was to participate in repairing radiation-induced breaks in double-stranded DNA. It is though that mutations in BRCA1 or BRCA2 might disable this mechanism, leading to more errors in DNA replication and ultimately to cancerous growth.

Breast Cancer Detection - reduce mortality is through early detection (general screening of the population for BRCA1 and BRCA2 is not yet recommended). New strategies to find anti-cancer drugs are constantly being developed. The latest, called 'synthetic lethal screening' looks for new drug targets in organisms such as yeast and fruit flies. In the same way that studies in yeast recently helped to identify the functions of BRCA1 and BRCA2, it is thought that drugs that work in more primative organisms will also be applicable to humans.

Mammary Glands-Pregnancy

- raised estrogens and progesterone stimulate gland development
- hemispherical shape due to fat deposition
- lactation supports development

Breast Abnormalities

occurs in 1% of female population
polymastia - extra breast
polytheli - extra nipple, supernumerary nipple (relatively common in males)

Glands

Hair

Before birth we have embryonic hair that has an imporant role in binding the skins waxy protective coating against our watery environment.
After birth we have early postnatal hair that is gradually replaced by the mature form.
At puberty we have a second round of hair formation under endocrine regulation by sex hormones.

Fetal Hair

Month 5 - hair appears on the head and beginning of vernix caseosa deposition.
Month 6 - body is covered by fine hairs (lanugo) and the deposit of vernix caseosa is considerable. Skin papilla are developed and the free border of the nail projects from the corium of the dermis.
Month 8 - skin now completely coated with vernix caseosa, and the lanugo begins to disappear. Skin is also pink in colour and subcutaneous fat being deposited (hypodermis layer).
Month 9 - lanugo has largely disappeared from the trunk.

Teeth

integumentary system specialization by epitheilal/mesenchymal interactions in development and develops with a major contribution from the neural crest.
- ectoderm of the first pharyngeal arch and neural crest, ectomesenchymal cells

Links

UNSW Embryology - Introduction | Detailed Overview of Skin components | Abnormalities | Stage 13/14 | Stage 22 | Histology | Dermatomes | Glands | Mammary Glands | Teeth | Hair | Nails

References

Before We Are Born (5th ed.) Moore and Persaud Chapter 21: P481-496
Essentials of Human Embryology Larson Chapter 14: P303-315
Color Atlas of Clinical Embryology Moore Persaud and Shiota Chapter 15: p231-236

Nature - Milestones in Cutaneous Biology "highlights groundbreaking advances in cutaneous biology over the past 100 years."
International Journal Developmental Biology 2004 - Skin Development special issue

Images

Hair histology
Dermatomes
Neonate hair

Glossary Links

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Course Content 2009

Cite this page: Hill, M.A. (2026, October 28) Embryology 2009 Lecture 18. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/2009_Lecture_18

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