Integumentary System Development

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Contents

Introduction

Skin Cartoon

The integumentary system covers the surface of the embryo (skin) and its specialized skin structures including hair, nails, sweat glands, mammary glands and teeth. As a system it has contributions from all embryonic layers.

The skin provides a barrier between ourselves and our environment, it also contains specializations in different regions including hair, nails, glands and sensory receptors. In other species, additional specializations such as feathers, horns and shell can be seen.

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 other epithelial specializations arose that are now located inside the body.

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. Fetal skin also has the ability to heal wounds without a scar in contrast to adult skin, this may relate to differences in the fetal extracellular matrix structure.


Integumentary Links: Introduction | Lecture | Hair | Tooth | Nail | Gland | Mammary Gland | Eyelid | Outer Ear | Touch | Histology | Abnormalities | Category:Integumentary
Historic Embryology: 1910 Manual of Human Embryology | 1923 Head Subcutaneous Plexus | 1921 Text-Book of Embryology | Historic Disclaimer

Some Recent Findings

  • Comparison between human fetal and adult skin[1] Healing of early-gestation fetal wounds results in scarless healing. Since the capacity for regeneration is probably inherent to the fetal skin itself, knowledge of the fetal skin composition may contribute to the understanding of fetal wound healing. The aim of this study was to analyze the expression profiles of different epidermal and dermal components in the human fetal and adult skin."
  • The integumentary skeleton of tetrapods: origin, evolution, and development[2] "Three types of tetrapod integumentary elements are recognized: (1) osteoderms, common to representatives of most major taxonomic lineages; (2) dermal scales, unique to gymnophionans; and (3) the lamina calcarea, an enigmatic tissue found only in some anurans."

Textbooks

Adult epidermis structure. See also molecular markers[3]
  • Human Embryology (2nd ed.) Larson Chapter 14 p443-455
  • The Developing Human: Clinically Oriented Embryology (6th ed.) Moore and Persaud Chapter 20: P513-529
  • Before We Are Born (5th ed.) Moore and Persaud Chapter 21: P481-496
  • Essentials of Human Embryology Larson Chapter 14: P303-315
  • Human Embryology, Fitzgerald and Fitzgerald
  • Color Atlas of Clinical Embryology Moore Persaud and Shiota Chapter 15: p231-236

Objectives

  • Understand the 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.

Development Overview

Human Embryo (Week 8, Stage 22) Integument

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

Fetal integumentary histology 01.jpg

Fetal human integumentary histology[1] (Weeks in figure are from LMP)

  • Basal cell - proliferation generates folds in basement membrane.
  • Neural crest cells - melanoblasts migrate into epithelium. These are the future melanocyte 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.

Embryonic and Fetal Epidermis

Electron Micrographs of the Developing Human Epidermis[4]

Human embryo skin 8-9 week EGA.jpg

6 to 8 weeks (8-9 week EGA)

Human embryo skin 9-11 week EGA.jpg

7 to 9 weeks (9-11 week EGA)

Human embryo skin 24 week EGA.jpg

22 weeks (about 24 week EGA)

Fetal Dermis

Fetal Dermis (18 wk LMP)[1]

The following data is from an immunohistological study of fetal skin dermis layer.[1]

  • Collagen type I is the principal component of extracellular matrix (ECM) (also in adult skin).
  • Collagen type III high ratio to collagen type I (than adult skin).
  • Glycosaminoglycans (GAGs) level higher (than adult skin).
  • Hyaluronic acid and chondroitin sulfate both higher.
  • Elastin was not present (found in adult skin).

Vernix Caseosa

Has several different potential functions and a variable composition.[5]

  • a highly variable coating of the fetal skin
  • high water content (80%) largely compartmentalized within fetal corneocytes (cells forming the stratum corneum)
  • develops cranio-caudally production coincides in utero with terminal differentiation of the epidermis and formation of the stratum corneum
  • primarily composed of sebum, cells that have sloughed off the fetus's skin and shed lanugo hair
  • can be absent in preterm infants
  • dehydration and rehydration processes occur two to four times faster at 37 degrees celcius than at room temperature[6]
  • towards term fragments of vernix can mix into the amniotic fluid resulting in (normal) turbidity
  • fetal swallowing of amniotic fluid mixed with fragments of vernix can also occur


Links: Gland Development

Adult Epidermal Stem Cells

In adult human skin epithelium, keratinocytes take about a month to differentiate from the basal stem cell layer, through the different stages of differentiation and layers, to be finally sloughed off on the surface. As well as keratinocyte differentiation, this represents a specialised form of programmed cell death called "cornification".

Epidermis stem cell models[3]

The following information is from a recent study on mouse skin using a single cell labelling system with longitudinal tracing and confocal imaging.[7]

Organization of the epidermis. Hair follicles contain stem cells located in the bulge (b, green), with the potential to generate lower hair follicle (lf), sebaceous gland (sg, orange) upper follicle (uf) and interfollicular epidermis (IFE, beige). The schematic shows the organization of keratinocytes in the IFE, as proposed by the stem/TA cell hypothesis. The basal layer comprises stem cells (S, blue), transit amplifying cells (TA, dark green), and post-mitotic basal cells (red), which migrate out of the basal layer as they differentiate (arrows).

Hair follicle development.jpg

Projected Z-stack confocal images of IFE wholemounts from AhcreERT R26EYFP/wt mice viewed from the basal surface at the times shown following induction. Yellow, EYFP; blue, DAPI nuclear stain. Scale bar, 20 microns.

Reprinted by permission from Macmillan Publishers Ltd: Nature. 2007 Mar 8;446(7132):185-9, copyright (2007)

Adult epidermal stem cells[7] "According to the current model of adult epidermal homeostasis, skin tissue is maintained by two discrete populations of progenitor cells. ...Here we show that clone-size distributions are consistent with a new model of homeostasis involving only one type of progenitor cell. These cells are found to undergo both symmetric and asymmetric division at rates that ensure epidermal homeostasis."


Links: MRC - Phil Jones Laboratory

Melanocytes

Melanoblast migration.png
Mouse-melanoblast migration icon.jpg
 ‎‎Mouse Melanoblast
Page | Play

See also Modeling melanoblast development [8]

Links: Neural Crest Development

Keratin

Cytoskeleton intermediate filament protein of epithelial cells required for cell mechanical stability and integrity, humans have 54 functional keratin genes.

Intermediate Filaments Type I

Acidic keratins (pI < 5.7) 40–64 kDa (n = 28)

  • K9-28 (epithelia)
  • K31-40 (hair/nail)

Intermediate Filaments Type II

Basic keratins (pI ≥ 6.0) 53–67 kDa (n = 26)

  • K1-8, K71-80 (epithelia)
  • K81-86 (hair/nail)
  • Keratins form heterodimers that assemble into heteropolymeric keratin filaments

Elaine Fuchs

Elaine Fuchs

A key researcher in the understanding of skin and keratin development Elaine Fuchs: A love for science that's more than skin deep. Interviewed by Ben Short[9] "Elaine Fuchs has collected many awards in her 30 years researching mammalian skin development, but it's hard to beat the two prizes she received in late 2009. Shortly before winning the prestigious L'Oreál-UNESCO award for women in science, Fuchs was awarded the National Medal of Science—the US's highest honor for outstanding scientific contributions."

Links: Lecture Cytoskeleton - Intermediate Filaments

Integrin Expression

The data below form a research article identifies expression of integrin subunits during development of human palm and sole skin.[10]

  • All of the integrins expressed during development were also present in mature epidermis and were largely confined to the basal layer of keratinocytes in a pericellular distribution.
  • alpha 3 and beta 1 subunits - were expressed prior to the initiation of stratification and did not change in abundance or distribution during subsequent development.
  • alpha 4 and beta 3 - were not detected at any time in the epidermis.

Every other subunit examined showed spatial or temporal changes in expression.

  • alpha 1 - was strong before stratification and until mid-development, but was greatly decreased in neonatal epidermis.
  • alpha 2 - was first detected in small patches of basal cells prior to stratification, and thereafter was found in the entire basal layer, with greater staining in developing sweat glands.
  • alpha 5 - was not expressed until mid-development, and then primarily in developing sweat glands, with faint expression in neonatal epidermis.
  • alpha v - was detected following stratification, in developing sweat glands, and occasionally in neonatal epidermis.
  • alpha 6 and beta 4 - were peribasally expressed before stratification. After stratification became concentrated at the basal cell surface in contact with the basement membrane, co-localizing with hemidesmosomes.

Three known ligands for keratinocyte integrins

  • laminin and collagen type IV - present in the basement membrane zone at all stages of development
  • fibronectin - only evident until about 13 weeks estimated gestational age.


Langerhans Cells

Langerhans cells (LCs) are immune system dendritic cells (antigen-presenting immune cells) found in the basal/suprabasal layers of stratified epidermis (and also in mucosal tissues). In the embryo LC precursors initially populate the single-layered epidermis and then undergo proliferation before birth.[11]


Links: Immune System Development

References

  1. 1.0 1.1 1.2 1.3 Neeltje A Coolen, Kelly C W M Schouten, Esther Middelkoop, Magda M W Ulrich Comparison between human fetal and adult skin. Arch. Dermatol. Res.: 2010, 302(1);47-55 PMID:19701759 | PMC2799629 | Arch Dermatol Res
  2. Matthew K Vickaryous, Jean-Yves Sire The integumentary skeleton of tetrapods: origin, evolution, and development. J. Anat.: 2009, 214(4);441-64 PMID:19422424
  3. 3.0 3.1 Elaine Fuchs Skin stem cells: rising to the surface. J. Cell Biol.: 2008, 180(2);273-84 PMID:18209104 JCB
  4. B A Dale, K A Holbrook, J R Kimball, M Hoff, T T Sun Expression of epidermal keratins and filaggrin during human fetal skin development. J. Cell Biol.: 1985, 101(4);1257-69 PMID:2413039 | PMC2113922
  5. W L Pickens, R R Warner, Y L Boissy, R E Boissy, S B Hoath Characterization of vernix caseosa: water content, morphology, and elemental analysis. J. Invest. Dermatol.: 2000, 115(5);875-81 PMID:11069626
  6. Robert Rissmann, Hendrik W W Groenink, Gert S Gooris, Marion H M Oudshoorn, Wim E Hennink, Maria Ponec, Joke A Bouwstra Temperature-induced changes in structural and physicochemical properties of vernix caseosa. J. Invest. Dermatol.: 2008, 128(2);292-9 PMID:17671513
  7. 7.0 7.1 Elizabeth Clayton, David P Doupé, Allon M Klein, Douglas J Winton, Benjamin D Simons, Philip H Jones A single type of progenitor cell maintains normal epidermis. Nature: 2007, 446(7132);185-9 PMID:17330052
  8. Lionel Larue, Florian de Vuyst, Véronique Delmas Modeling melanoblast development. Cell. Mol. Life Sci.: 2013, 70(6);1067-79 PMID:22915137
  9. Elaine Fuchs Elaine Fuchs: A love for science that's more than skin deep. Interviewed by Ben Short. J. Cell Biol.: 2009, 187(7);938-9 PMID:20038675 | PMC2806278
  10. M D Hertle, J C Adams, F M Watt Integrin expression during human epidermal development in vivo and in vitro. Development: 1991, 112(1);193-206 PMID:1769328
  11. Nighat Yasmin, Thomas Bauer, Madhura Modak, Karin Wagner, Christopher Schuster, Rene Köffel, Maria Seyerl, Johannes Stöckl, Adelheid Elbe-Bürger, Daniel Graf, Herbert Strobl Identification of bone morphogenetic protein 7 (BMP7) as an instructive factor for human epidermal Langerhans cell differentiation. J. Exp. Med.: 2013; PMID:24190429


Reviews

Gurcharan Singh, G Archana Unraveling the mystery of vernix caseosa. Indian J Dermatol: 2008, 53(2);54-60 PMID:19881987


Articles

Sirkku Peltonen, Laura Raiko, Juha Peltonen Desmosomes in developing human epidermis. Dermatol Res Pract: 2010, 2010();698761 PMID:20592759

Maria Malminen, Sirkku Peltonen, Jussi Koivunen, Juha Peltonen Functional expression of NF1 tumor suppressor protein: association with keratin intermediate filaments during the early development of human epidermis. BMC Dermatol.: 2002, 2();10 PMID:12199909

B A Dale, K A Holbrook, J R Kimball, M Hoff, T T Sun Expression of epidermal keratins and filaggrin during human fetal skin development. J. Cell Biol.: 1985, 101(4);1257-69 PMID:2413039


Search PubMed

Search April 2010 "Integumentary Development" - All (86) Review (9) Free Full Text (18)

Search Pubmed: Integumentary Development | Skin Development | Hair Development | Tooth Development | Vernix Caseosa

Additional Images

Category:Integumentary

Terms

  • apocrine gland - (sweat gland) proteinaceous secretion associated with hair (axilla, areola, genital and anal regions). Additional glands associated with eyelashes are called the glands of Moll (ciliary gland).
  • arrector pili muscle - bundle of smooth muscle associated with hair follicle, inserts into the papillary layer of the dermis and attaches to the dermal sheath of the hair follicle.
  • bulb - the hair follicle enlargement located at its deepest end, dividing cells form the hair and the root sheath.
  • columnar - cells are longer than they are wide.
  • cuboidal - cells are about the same length and width.
  • cutis - alternative term for the epidermis and the dermis layers of the skin.
  • dermal papillae - interdigitation of the dermis with the epidermis.
  • dermis - connective tissue middle layer of the skin, consists of two sublayers (papillary and reticular layers) that do not have a clear boundary.
  • dermomyotome - Early embryonic dorsolateral half of the somite that will later divide to form both the dermatome and myotome. The dermatome will contribute the dermis and hypodermis of the skin. The myotome will contribute the skeletal muscle of muscoloskeletal system. Development sequence: mesoderm to paraxial mesoderm to somite to "dermomyotome" then dermatome and myotome. (More? Somitogenesis | Musculoskeletal System Development | Integumentary System Development)
  • dermatome - The early embryonic dorsal portion of the somite that will contribute the dermis and hypodermis of the skin. Note in the adult, this term is used to the skin sensory region innervated by a single spinal (nerve) segment. mesoderm - paraxial mesoderm - somite - dermomyotome - dermatome - dermis. (More? Somitogenesis | Musculoskeletal System Development | Integumentary System Development | Neural System Development)
  • epidermis - Histological term describing the external cellular epithelial layer of the integumentary (skin) covering the entire body. This surface layer of keratinocytes is ectoderm in origin, while the underlying connective tissue layers of dermis and hypodermis are mesoderm in origin. (More? Integumentary Development)
  • hair - (pili) in humans consists of vellus and terminal hairs.
  • holocrine - form of gland secretion where the secretory cells eventually lyse (rupture) and are lost. On the skin these cells release sebum consisting mainly of lipid.
  • hypodermis - (subcutis) connective tissue inner layer of the skin that binds it to underlying structures.
  • integumentary - term for the skin and its appendages.
  • melanin - (Greek, melanos = black) The pigment produced by melanocytes that provides photoprotection, preventing cellular DNA damage, and colouring of the basal epithelial cells that absorb the pigment.
  • melanoblast - (Greek, melanos = black) The neural crest precursor cell that differentiates to form melanocytes located in the skin and other tissues that produces melanin. (More? Neural Crest Development | Integumentary System Development)
  • melanocyte - (Greek, melanos = black) A pigmented cell, neural crest in origin, differentiating from melanoblasts located in the skin and other tissues that produces melanin. The melanocytes within the integument (skin) transfer melanin to keratinocytes to give skin colour and to the hair follicle to give hair colour. Melanocytes are also located within "non-cutaneous" tissues in the eye (for eye colour), harderian gland and inner ear. This is the cell type that proliferates in the cancer melanoma. (More? Neural Crest Development | Integumentary System Development)
  • merkel cell - An epidermal-derived cell in touch-sensitive area of the epidermis and mediate mechanotransduction in the skin. Previously thought to be neural crest in origin, but recently shown to arise from the embryonic epithelium. The cells are named after Friedrich Sigmund Merkel, a German anatomist who was the first to describe them in 1875. (More? Lecture - Integumentary Development | PMID 19786578 | PMID 3782861)
  • merocrine gland - (sweat gland, eccrine sweat) simple tubular glands located at the border between the dermis and hypodermis. These glands regulate the body temperature.
  • papillary layer - dermis sublayer that appears less dense and contains more cells lying close beneath the epidermis.
  • reticular layer - dermis sublayer that appears denser and contains fewer cells with thick collagen bundles lying parallel to the skin surface.
  • root sheath - cell layers that surround the hair.
  • sebaceous gland - holocrine gland associated with both the hair follicle and hairless parts of the skin (lips, cheek oral surface and external genitalia). Embedded in the dermis and are sites of infections (acne).
  • simple - consisting of a single cell layer.
  • squamous - flattened.
  • stratified - consisting of several cell layers.
  • terminal hairs - hair seen in obviously hairy parts of the body.
  • thick skin - refers to the skin histology found on the palms of the hand and soles of the feet, do not contain hair. Note that this is used as a histological term not a measurement of overall skin thickness.
  • thin skin - refers to the skin histology found on skin in all other regions beside palms and soles.
  • vellus hairs - fine short hairs only lightly pigmented covering the body.



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Cite this page: Hill, M.A. (2014) Embryology Integumentary System Development. Retrieved April 23, 2014, from http://embryology.med.unsw.edu.au/embryology/index.php?title=Integumentary_System_Development

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Dr Mark Hill 2014, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G
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