UNSW Embryology

Integumentary Development - Hair

© Dr Mark Hill (2011)

Acknowledgements

Introduction

Page Links: Introduction | Some Recent Findings | Development Overview | Lanugo Hair | Neonatal Hair | Molecular Hair Development | Sonic Hedgehog Pathway | Pattern Formation Skin | Puberty Hair Development | Hair Loss | References | WWW Links | Terms | Glossary

Some Recent Findings

Hair Follicle Pattern Formation there are two stage dependent ways of regulating pattern formation. Wang Y, Badea T, Nathans J. Order from disorder: Self-organization in mammalian hair patterning. Proc Natl Acad Sci U S A. 2006 Dec 26;103(52):19800-5. Epub 2006 Dec 15.

"These experiments define two systems for hair orientation: a global orienting system that acts early in development and is Fz6-dependent, and a local self-organizing system that acts later and is Frizzled 6 (Fz6) independent." PNAS Link | PubMed Link

Hair Follicle Pattern Formation a study has looked at the signaling pathway involved in establishing the regular patterning of hair follicles using embryonic skin cultures.

"We find that ectodysplasin receptor (Edar)–bone morphogenetic protein (BMP) signaling and transcriptional interactions are central to generation of the primary hair follicle pattern, with restriction of responsiveness, rather than localization of an inducing ligand, being the key driver in this process." PNAS Link

Development Overview

Embryonic

• follicle forms in stratum germinativum of epidermis
• hair bud -> hair bulb
• hair bulb forms hair
• mesenchyme forms hair papilla
• germinal matrix cells become keratinized to form hair shaft
• week 12 - lanugo hair (Latin, lana = wool) - first hair formed replaced postnatally, role in binding vernix to skin

Puberty

Coarse hair in pubis and axilla in both male and female (in males also on face and other body regions chest, etc) (More? Puberty Hair Development | Puberty Notes)

Hair Colour

melanocytes produce melanin which influences hair colour.

Arrector Pili Muscle

develop in mesenchyme and form the muscles that move hair.

Lanugo Hair

From about the third month lanugo hair (Latin, lana = wool) hiar is initially formed and it has a role in binding vernix to skin.

Hair grows over the entire body at the same rate, so the hairs are the same length, and is shed abut 4 weeks before birth. Premature infants can still be covered with these hairs.

Neonatal Hair

Newborn infants have two types of hair:

Vellus Hairs

short hairs, only a centimetre or two long, and contain little or no pigment

follicles that produce them do not have sebaceous glands and never produce any other kind of hairs

Terminal Hairs

long hairs that grow on the head and in many people on the body, arms and legs

produced by follicles with sebaceous glands

the hairs in these follicles gradually become thinner and shorter until they look like vellus hairs

Hair Follicle

Hair Follicle Phases

There are two main hair follicle phases.

Anagen Phase: active

Catagen Phase: apoptosis-driven involution

Molecular Hair Development

Signaling pathways in follicle formation:

Shh and its effectors

antagonists for the Wnt (Dkk4)

BMP (Sostdc1)

variant NF-kappaB-signaling cascade, based on lymphotoxin-beta (LTbeta)/RelB.

(See Cui CY, Hashimoto T, Grivennikov SI, Piao Y, Nedospasov SA, Schlessinger D. Ectodysplasin regulates the lymphotoxin-{beta} pathway for hair differentiation. Proc Natl Acad Sci U S A. 2006 May 31)

Signaling inhibitors of hair/follicle formation: EGF, FGF5

Sonic Hedgehog Pathway

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

SHH Activation (inappropriate)

• 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

Pattern Formation Skin

• In birds, the main appendages are the feathers and the foot scales. Their formation results from a series of inductive events between ectoderm (later epidermis) and subectodermal mesoderm (later individualized dermis).
• Morphogenetically, the mesodermal (mesenchymal) component of skin is the predominant tissue, insofar as it controls most morphological and physiological features of developing skin and appendages, notably transformation of ectoderm into epidermis, polarization, proliferation and stratification of epidermal cells, initiation, site, size and distribution pattern of epidermal placodes, species-specific architecture of appendages, regional specification of keratin synthesis.
• The ectodermal (epithelial) component is able to respond to the mesodermal inductive instructions by building feathers and scales in conformity with the specific origin of the dermis. In these epithelial-mesenchymal interactions, extracellular matrix and the microarchitecture of the dermal-epidermal junction appear to play an important role.

Extracellular matrix components

• (primarily collagens, proteoglycans and adhesive glycoproteins) and dermal cell processes close to the epidermal basement membrane become distributed in a microheterogeneous fashion, thus providing a changing substratum for the overlying epidermis. It is assumed that the latter is able to somehow sense the texture and composition of its substratum, and by doing so to appropriately engage in the formation of glabrous, feathered or scaly skin.
• Sengel P Int J Dev Biol 1990 Mar;34(1):33-50

Puberty Hair Development

The appearance of pubic hair occurs along with ther secondary sexual characteristics (being also staged similarly) and is under endocrine control.

Estrogens- (1 beta-estradiol, E2) involved in skin physiology and are potent hair growth modulators.

Testosterone- Face, trunk and extremities increases hair follicle anagen phase (active) and increases also hair growth rate, thickness, medullation and pigmentation. Effects due to high hormone levels and target organ conversion to 5 alpha-dihydrotestosterone. Pubic hair develops even in absence of 5 alpha-reductase effect. (Ebling FJ., 1986)

Tanner Stages

Table based upon the Tanner stages of secondary sexual development. (Tanner JM. Growth at Adolescence. 2nd ed. Oxford: Blackwell Scientific, 1962.)

Hair Loss

In development the initial hair is lost. In the adult hair loss, or "alopecia", has three distinct forms:

androgenetic alopecia - male- and female-pattern hair loss.

telogen effluvium - alteration of the normal hair cycle, due to many different stress stimuli (severe stress, chemotherapy, childbirth, major surgery, severe chronic illness, rarely occurance in vaccination)

alopecia areata - autoimmune disease, form antibodies against some hair follicles, distinct circular pattern of hair loss.

References

Reviews | Articles | Search NCBI Bookshelf | Search PubMed

Reviews

Peters EM, Arck PC, Paus R. Hair growth inhibition by psychoemotional stress: a mouse model for neural mechanisms in hair growth control. Exp Dermatol. 2006 Jan;15(1):1-13.

Sundberg JP, Peters EM, Paus R. Analysis of hair follicles in mutant laboratory mice. J Investig Dermatol Symp Proc. 2005 Dec;10(3):264-70.

Botchkarev VA, Fessing MY. Edar signaling in the control of hair follicle development. J Investig Dermatol Symp Proc. 2005 Dec;10(3):247-51.

Stenn KS, Cotsarelis G. Bioengineering the hair follicle: fringe benefits of stem cell technology. Curr Opin Biotechnol. 2005 Oct;16(5):493-7.

Schmidt-Ullrich R, Paus R. Molecular principles of hair follicle induction and morphogenesis. Bioessays. 2005 Mar;27(3):247-61.

Ahmad W, Panteleyev AA, Christiano AM. The molecular basis of congenital atrichia in humans and mice: mutations in the hairless gene. J Investig Dermatol Symp Proc. 1999 Dec;4(3):240-3.

Ebling FJ. Hair follicles and associated glands as androgen targets. Clin Endocrinol Metab. 1986 May;15(2):319-39.

Articles

Wang Y, Badea T, Nathans J. Order from disorder: Self-organization in mammalian hair patterning. Proc Natl Acad Sci U S A. 2006 Dec 26;103(52):19800-5. Epub 2006 Dec 15. PNAS Link

Ouji Y, Yoshikawa M, Shiroi A, Ishizaka S. Promotion of hair follicle development and trichogenesis by Wnt-10b in cultured embryonic skin and in reconstituted skin. Biochem Biophys Res Commun. 2006 Jun 30;345(2):581-7.

Cui CY, Hashimoto T, Grivennikov SI, Piao Y, Nedospasov SA, Schlessinger D. Ectodysplasin regulates the lymphotoxin-{beta} pathway for hair differentiation. Proc Natl Acad Sci U S A. 2006 May 31

Search NCBI Bookshelf: Bookshelf - hair development

Developmental Biology - Development of the hair follicles in fetal human skin | Eurekah Bioscience Collection - Role of GLI proteins in embryonic hair follicle development | Molecular Biology of the Cell - FGF5 is a negative regulator of hair formatio

Search PubMed: Search May 2006 "hair development" 6,574 reference articles of which 813 were reviews.

Search term = hair development | hair follicle development | lanugo hair

Terms

anagen - hair follicle active growth phase, hair follicle progenitors derived from the bulge interact with the mesenchymal dermal papilla cells to generate the lineages of the hair follicle.

catagen - end of active growing phase of the life cycle of the hair, between growing phase (anagen) and resting stage (telogen).

telogen - hair follicle resting phase of hair growth cycle.

Glossary of Terms

A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | Numbers | Old Glossary

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