Integumentary System - Hair Development

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Introduction

Hair follicle cartoon

Hair formation, hair follicle or pilli development, is an excellent example of two distinct developmental processes: epithelio-mesenchymal interactions and pattern formation. The differentiated hair follicle will eventually contain 20 or more different cell types. Melanocytes, which provide the hair colour, have a neural crest origin, and with ageing their numbers decline leading to whitening (grey) of the hair process.

Hair follicle development in humans begins as an epithelial-mesenchymal interaction at week 9 - 12. This initial lanugo hair is replaced in the late fetal or early neonate by vellus and terminal hairs. A second round of development occurs during puberty under the influence of steroidal hormones.

The hair follicle is also a site for stem cells, allowing replacement of the follicle.


Integumentary Links: integumentary | Lecture | hair | tooth | nail | integumentary gland | mammary gland | vernix caseosa | melanocyte | touch | Eyelid | outer ear | Histology | integumentary abnormalities | Category:Integumentary
Hair Links  
Hair Links: Overview | Lanugo | Neonatal | Vellus | Terminal | Hair Follicle | Follicle Phases | Stem Cells | Molecular | Pattern | Puberty | Histology | Hair Colour | Arrector Pili Muscle | Hair Loss | Integumentary
Touch Links  
Touch Links: Touch Receptors | Touch Pathway | Pacinian Corpuscle | Meissner's Corpuscle | Merkel Cell | Sensory Modalities | Neural Crest Development | Neural System Development | Student project | Integumentary | Sensory System
Historic Embryology  
1910 Manual of Human Embryology | 1914 Integumentary | 1923 Head Subcutaneous Plexus | 1921 Text-Book of Embryology | 1924 Developmental Anatomy | 1941 Skin Sensory | Historic Disclaimer
Tinycc  
http://tiny.cc/Integument_Development


Historic: 1910 Hair

Some Recent Findings

  • Mutations in TSPEAR, Encoding a Regulator of Notch Signaling, Affect Tooth and Hair Follicle Morphogenesis[1] "In the present study, we aimed at elucidating the genetic basis of a new form of ED featuring facial dysmorphism, scalp hypotrichosis and hypodontia. Using whole exome sequencing, we identified 2 frameshift and 2 missense mutations in TSPEAR segregating with the disease phenotype in 3 families. TSPEAR encodes the thrombospondin-type laminin G domain and EAR repeats (TSPEAR) protein, whose function is poorly understood. TSPEAR knock-down resulted in altered expression of genes known to be regulated by NOTCH and to be involved in murine hair and tooth development. Pathway analysis confirmed that down-regulation of TSPEAR in keratinocytes is likely to affect Notch signaling. Accordingly, using a luciferase-based reporter assay, we showed that TSPEAR knock-down is associated with decreased Notch signaling. In addition, NOTCH1 protein expression was reduced in patient scalp skin. Moreover, TSPEAR silencing in mouse hair follicle organ cultures was found to induce apoptosis in follicular epithelial cells, resulting in decreased hair bulb diameter."
  • ILK modulates epithelial polarity and matrix formation in hair follicles.[2] "We show that in the absence of ILK, the hair follicle matrix lineage fails to develop, likely due to abnormalities in development of apical-basal cell polarity, as well as in laminin-511 and basement membrane assembly at the tip of the hair bud. These defects also result in impaired specification of hair matrix and absence of precortex and inner sheath root cell lineages. The molecular pathways affected in ILK-deficient follicles are similar to those in the absence of epidermal integrin β1 and include Wnt, but not sonic hedgehog, signaling. ILK-deficient hair buds also show abnormalities in the dermal papilla."
  • Embryonic development of hair follicle pluripotent stem (hfPS) cells.[3] "We have shown that nestin-positive and K15-negative multipotent hair follicle stem cells are located above the hair follicle bulge, and we termed these cells hair follicle pluripotent stem (hfPS) cells."
More recent papers  
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This table shows an automated computer PubMed search using the listed sub-heading term.

  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
  • References appear in this list based upon the date of the actual page viewing.

References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.

Links: References | Discussion Page | Pubmed Most Recent | Journal Searches


Search term: Hair Embryology

Mohamed M A Abumandour Ultrastructure features of the surface of the gills and the lower pharyngeal jaw of the Tilapia Zilli, redbelly tilapia (Coptodon Zillii, Gervais, 1848). Anat Histol Embryol: 2018; PubMed 30474141

Haleh Mokabber, Nowruz Najafzadeh, Mohammad Mohammadzadeh Vardin miR-124 promotes neural differentiation in mouse bulge stem cells by repressing Ptbp1 and Sox9. J. Cell. Physiol.: 2018; PubMed 30417370

Erin A Greguske, Maria Carreres-Pons, Blanca Cutillas, Pere Boadas-Vaello, Jordi Llorens Calyx junction dismantlement and synaptic uncoupling precede hair cell extrusion in the vestibular sensory epithelium during sub-chronic 3,3'-iminodipropionitrile ototoxicity in the mouse. Arch. Toxicol.: 2018; PubMed 30377733

Zuhong He, Qiaojun Fang, He Li, Buwei Shao, Yuan Zhang, Yuhua Zhang, Xiao Han, Rongrong Guo, Cheng Cheng, Lingna Guo, Lusen Shi, Ao Li, Chenjie Yu, Weijia Kong, Chunjie Zhao, Xia Gao, Renjie Chai The role of FOXG1 in the postnatal development and survival of mouse cochlear hair cells. Neuropharmacology: 2018; PubMed 30336149


Hind M Almohanna, Azhar A Ahmed, John P Tsatalis, Antonella Tosti The Role of Vitamins and Minerals in Hair Loss: A Review. Dermatol Ther (Heidelb): 2018; PubMed 30547302

Heuijoon Park, Sonali Lad, Kelsey Boland, Kelly Johnson, Nyssa Readio, Guangchun Jin, Samuel Asfaha, Kelly S Patterson, Ashok Singh, Xiangdong Yang, Douglas Londono, Anupama Singh, Carol Trempus, Derek Gordon, Timothy C Wang, Rebecca J Morris Bone marrow-derived epithelial cells and hair follicle stem cells contribute to development of chronic cutaneous neoplasms. Nat Commun: 2018, 9(1);5293 PubMed 30546048

Christos Petridis, Alexander A Navarini, Nick Dand, Jake Saklatvala, David Baudry, Michael Duckworth, Michael H Allen, Charles J Curtis, Sang Hyuck Lee, A David Burden, Alison Layton, Veronique Bataille, Andrew E Pink, Acne Genetic Study Group, Isabelle Carlavan, Johannes J Voegel, Timothy D Spector, Richard C Trembath, John A McGrath, Catherine H Smith, Jonathan N Barker, Michael A Simpson Genome-wide meta-analysis implicates mediators of hair follicle development and morphogenesis in risk for severe acne. Nat Commun: 2018, 9(1);5075 PubMed 30542056

Weiming Qiu, Cheng-Ming Chuong, Mingxing Lei Regulation of melanocyte stem cells in the pigmentation of skin and its appendages: Biological patterning and therapeutic potentials. Exp. Dermatol.: 2018; PubMed 30537004

Older papers  
These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table.

See also the Discussion Page for other references listed by year and References on this current page.

  • Biology and genetics of hair.[4] "The mammalian hair follicle (HF) is a complex structure composed of several distinct cell layers. The HF is an ectodermal appendage that resides in the skin, and unlike other tissues and organs, it possesses the remarkable ability to self-renew and undergoes a hair cycle that persists in adult life. Stem cells in the bulge region of the HF, as well as dermal papilla cells, play key roles in the regulation of successive hair cycles."

Textbooks

  • 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

Histology

Adult hair histology.

Integumentary- hair follicle 01.jpg Integumentary- hair follicle 02.jpg

Development Overview

Hair development stages.jpg

Embryonic

thumb|Hair follicle stem cells

  • 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)

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

Neonate 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

On the head, there are also two periods of hair development in which hair growth begins at the forehead and then extends to the back of the neck.

Then at 2- 3 months old, the first hairs may be shed naturally over an area on the back of the head. This is often mistakenly thought to be due to head rubbing.

Eyelash Hairs

The eyelash hairs function to protect and maintain the health of the lid margin. The adult eyelash hair follicles: produce shorter hair shafts, have no arrector pili muscle, and have a shorter hair cycle.[5] See also a recent review.[6] The eyelid also contains in addition to eyelashes, a number of unique integumentary glands.


Hair Follicle

Hair histology

This image shows a histological section through the adult skin showing "slices" through 4 hair follicles and their associated glands in different planes. The hair shaft is the yellow structure extending from the bulb within the hair follicle.

From the top down the three major skin layers shown are:

epidermis (red upper region) surface ectoderm in origin, epithelium containing keratinocytes

dermis (dark blue middle region) mesoderm in origin, connective tissue containing many different cell types and collagen fibers.

hypodermis (pale lower region) mesoderm in origin, connective tissue containing many adipose cells.

Hair Follicle Phases

There are several phases of hair follicle growth.

  • Anagen Phase - active phase
  • Catagen Phase - apoptosis-driven involution, end of active growing phase of the life cycle of the hair, between growing phase (anagen) and resting stage (telogen).
  • Telogen Phase - hair follicle resting phase of hair growth cycle.

Hair Follicle Stem Cells

Hair follicles contain stem cells located in the bulge[7]

Hair follicles contain stem cells located in the bulge[7]

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.

ctodysplasin regulates the lymphotoxin-{beta} pathway for hair differentiation.[8]

Signaling inhibitors of hair/follicle formation: EGF, FGF5


Wnt signaling

  • Initiation and maintenance of hair morphogenesis
  • Wnt3a induce hair formation
  • Wnt10b promotes hair neogenesis

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. ...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.[9]

Tanner Stages


  Stage   Pubic Hair Development
  1   None
  2   Few darker hairs along labia or at base of penis
  3   Curly pigmented hairs across pubes
  4   Small adult configuration
  5   Adult configuration with spread onto inner thighs
  6   Adult configuration with spread to linea alba

Table based upon the Tanner stages of secondary sexual development.[10]

Histology

Hair Colour

Melanocytes produce melanin which influences hair colour.

Arrector Pili Muscle

Arrector Pili Muscle

These mesoderm-derived small smooth muscles (hair erector muscle) are associated with the hair (pilosebaceous unit). Their muscle innervation is mainly by noradrenergic fibers and minor cholinergic. Muscle contraction is in response to response to cold or emotional state causes the hair to stand erect ("goosebump").

Muscle Attachments[11]

  • proximal end - anchor the bulge areas of hair follicle.
  • distal end - situated in the upper dermis.

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.

Abnormalities

References

  1. Peled A, Sarig O, Samuelov L, Bertolini M, Ziv L, Weissglas-Volkov D, Eskin-Schwartz M, Adase CA, Malchin N, Bochner R, Fainberg G, Goldberg I, Sugawara K, Baniel A, Tsuruta D, Luxenburg C, Adir N, Duverger O, Morasso M, Shalev S, Gallo RL, Shomron N, Paus R & Sprecher E. (2016). Mutations in TSPEAR, Encoding a Regulator of Notch Signaling, Affect Tooth and Hair Follicle Morphogenesis. PLoS Genet. , 12, e1006369. PMID: 27736875 DOI.
  2. Rudkouskaya A, Welch I & Dagnino L. (2014). ILK modulates epithelial polarity and matrix formation in hair follicles. Mol. Biol. Cell , 25, 620-32. PMID: 24371086 DOI.
  3. Amoh Y, Li L, Katsuoka K & Hoffman RM. (2010). Embryonic development of hair follicle pluripotent stem (hfPS) cells. Med Mol Morphol , 43, 123-7. PMID: 20683701 DOI.
  4. Shimomura Y & Christiano AM. (2010). Biology and genetics of hair. Annu Rev Genomics Hum Genet , 11, 109-32. PMID: 20590427 DOI.
  5. Paus R, Burgoa I, Platt CI, Griffiths T, Poblet E & Izeta A. (2016). Biology of the eyelash hair follicle: an enigma in plain sight. Br. J. Dermatol. , 174, 741-52. PMID: 26452071 DOI.
  6. Aumond S & Bitton E. (2018). The eyelash follicle features and anomalies: A review. J Optom , 11, 211-222. PMID: 30017866 DOI.
  7. 7.0 7.1 Clayton E, Doupé DP, Klein AM, Winton DJ, Simons BD & Jones PH. (2007). A single type of progenitor cell maintains normal epidermis. Nature , 446, 185-9. PMID: 17330052 DOI.
  8. Cui CY, Hashimoto T, Grivennikov SI, Piao Y, Nedospasov SA & Schlessinger D. (2006). Ectodysplasin regulates the lymphotoxin-beta pathway for hair differentiation. Proc. Natl. Acad. Sci. U.S.A. , 103, 9142-7. PMID: 16738056 DOI.
  9. F J Ebling Hair follicles and associated glands as androgen targets. Clin Endocrinol Metab: 1986, 15(2);319-39 PubMed 3521958
  10. Tanner JM. Growth at Adolescence. 2nd ed. Oxford: Blackwell Scientific, 1962.
  11. Narisawa Y, Hashimoto K & Kohda H. (1996). Merkel cells participate in the induction and alignment of epidermal ends of arrector pili muscles of human fetal skin. Br. J. Dermatol. , 134, 494-8. PMID: 8731675


Journals

Reviews

Shimomura Y. (2016). Journey toward unraveling the molecular basis of hereditary hair disorders. J. Dermatol. Sci. , 84, 232-238. PMID: 27523806 DOI.

Shimomura Y & Christiano AM. (2010). Biology and genetics of hair. Annu Rev Genomics Hum Genet , 11, 109-32. PMID: 20590427 DOI.

López-Bueno A, Villarreal LP & Almendral JM. (2006). Parvovirus variation for disease: a difference with RNA viruses?. Curr. Top. Microbiol. Immunol. , 299, 349-70. PMID: 16568906

Sundberg JP, Peters EM & Paus R. (2005). Analysis of hair follicles in mutant laboratory mice. J. Investig. Dermatol. Symp. Proc. , 10, 264-70. PMID: 16382678 DOI.

Articles

Search PubMed

Search Pubmed: Hair Development | hair follicle development |

Additional Images

Category:Integumentary

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.

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Cite this page: Hill, M.A. (2018, December 15) Embryology Integumentary System - Hair Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Integumentary_System_-_Hair_Development

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© Dr Mark Hill 2018, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G