Talk:2009 Lecture 18
Background Reading
hyponychium - the thickened epidermis beneath the free distal end of the claw of a digit. Hertwig’s Epithelial Root Sheath - (HERS) a bi-layered cell sheath surrounding the roots of amphibian teeth (e.g. in Triturus and Salamandra)(Hertwig, 1874). HERS descends from the oral epithelium and the enamel organ to form a collar around the cervical part of the amphibian tooth root. http://www.ncbi.nlm.nih.gov/pubmed/16450392
PLoS Biology
- An Ideal Society? Neighbors of Diverse Origins Interact to Create and Maintain Complex Mini-Organs in the Skin
- Molecular Dissection of Mesenchymal–Epithelial Interactions in the Hair Follicle
- Dorsoventral Patterning of the Mouse Coat by Tbx
- Regulation of Mammary Stem/Progenitor Cells by PTEN/Akt/β-Catenin Signaling
- An Integrated Gene Regulatory Network Controls Stem Cell Proliferation in Teeth
PMC
- Evolution and development of teeth. McCollum M, Sharpe PT. J Anat. 2001 Jul-Aug;199(Pt 1-2):153-9. Review. PMID: 11523817 PDF
- Role of homeobox genes in the patterning, specification, and differentiation of ectodermal appendages in mammals. Duverger O, Morasso MI. J Cell Physiol. 2008 Aug;216(2):337-46. Review. PMID: 18459147 J Cell Physiol. | Figure 1 Key steps in the development of three major ectodermal appendages
Molecular Nail Development
- Development 121, 1065-1076 (1995) Msx2 expression domain is always more distal than Msx1. At birth both Msx1 and Msx2 are expressed in cells of the nail bed and hair follicle.
Molecular Melanocyte Development
- Microphthalmia-associated transcription factor - (MITF) is a master gene regulating melanocyte development and functions as a “lineage addiction” oncogene in malignant melanoma.
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
Development of Skin
Skin is our largest organ, providing a protective layer between us and our environment
embryonic origins
- 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 skin- thin (most of body) thick (soles of feet and hands)
- week 4-5 single ectodermal layer
Epidermis
- initially periderm
- keratinization and desquamification
- replaced by basal cells
vernix caseosa (L. varnish)
- covers fetal skin- secretion from sebaceous glands
- protects skin from extraembryonic fluids amnion, urine
- slippery and helps with parturition
Epidermis
- 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 (Gr. melas= black) accounts for differet skin colour
Dermis and Blood Vessels
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
- form as ingrowth of ectoderm into 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
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
nail plate - visible part of the nail nail bed - skin beneath the nail plate cuticle - tissue that overlaps the plate and rims the base of the nail nail folds - skin folds that frame and support the nail on three sides lunula - half-moon at the base of the nail matrix - hidden part of the nail unit under the cuticle
