Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Accepted manuscripts
    • Issue in progress
    • Latest complete issue
    • Issue archive
    • Archive by article type
    • Special issues
    • Subject collections
    • Cell Scientists to Watch
    • First Person
    • Sign up for alerts
  • About us
    • About JCS
    • Editors and Board
    • Editor biographies
    • Travelling Fellowships
    • Grants and funding
    • Journal Meetings
    • Workshops
    • The Company of Biologists
    • Journal news
  • For authors
    • Submit a manuscript
    • Aims and scope
    • Presubmission enquiries
    • Fast-track manuscripts
    • Article types
    • Manuscript preparation
    • Cover suggestions
    • Editorial process
    • Promoting your paper
    • Open Access
    • JCS Prize
    • Manuscript transfer network
    • Biology Open transfer
  • Journal info
    • Journal policies
    • Rights and permissions
    • Media policies
    • Reviewer guide
    • Sign up for alerts
  • Contacts
    • Contact JCS
    • Subscriptions
    • Advertising
    • Feedback
  • COB
    • About The Company of Biologists
    • Development
    • Journal of Cell Science
    • Journal of Experimental Biology
    • Disease Models & Mechanisms
    • Biology Open

User menu

  • Log in

Search

  • Advanced search
Journal of Cell Science
  • COB
    • About The Company of Biologists
    • Development
    • Journal of Cell Science
    • Journal of Experimental Biology
    • Disease Models & Mechanisms
    • Biology Open

supporting biologistsinspiring biology

Journal of Cell Science

  • Log in
Advanced search

RSS   Twitter  Facebook   YouTube  

  • Home
  • Articles
    • Accepted manuscripts
    • Issue in progress
    • Latest complete issue
    • Issue archive
    • Archive by article type
    • Special issues
    • Subject collections
    • Cell Scientists to Watch
    • First Person
    • Sign up for alerts
  • About us
    • About JCS
    • Editors and Board
    • Editor biographies
    • Travelling Fellowships
    • Grants and funding
    • Journal Meetings
    • Workshops
    • The Company of Biologists
    • Journal news
  • For authors
    • Submit a manuscript
    • Aims and scope
    • Presubmission enquiries
    • Fast-track manuscripts
    • Article types
    • Manuscript preparation
    • Cover suggestions
    • Editorial process
    • Promoting your paper
    • Open Access
    • JCS Prize
    • Manuscript transfer network
    • Biology Open transfer
  • Journal info
    • Journal policies
    • Rights and permissions
    • Media policies
    • Reviewer guide
    • Sign up for alerts
  • Contacts
    • Contact JCS
    • Subscriptions
    • Advertising
    • Feedback
Cell Science at a Glance
The hair cycle
Laura Alonso, Elaine Fuchs
Journal of Cell Science 2006 119: 391-393; doi: 10.1242/jcs.02793
Laura Alonso
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Elaine Fuchs
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & tables
  • Info & metrics
  • PDF
Loading

The hair coat, which keeps most mammals warm, dry and protected from harmful elements, requires a constant supply of new hairs throughout the lifetime of the animal. To produce new hairs, existing follicles undergo cycles of growth (anagen), regression (catagen) and rest (telogen). During each anagen phase, follicles produce an entire hair shaft from tip to root; during catagen and telogen, follicles reset and prepare their stem cells so that they can receive the signal to start the next growth phase and make the new hair shaft. The hair cycle represents a remarkable model for studies of the regulation of stem cell quiescence and activation, as well as transit-amplifying cell proliferation, cell-fate choice, differentiation and apoptosis in a regenerative adult epithelial tissue. Here we summarize the major events of the hair cycle, and touch on known regulators of the transitions. Detailed reviews of the hair cycle and its regulation can be found elsewhere (Lavker et al., 2003; Millar, 2002; Muller-Rover et al., 2001).⇓

Figure1
  • Download figure
  • Open in new tab
  • Download powerpoint

Morphogenesis

In the embryo, the skin begins as a single layer of epidermal stem cells. Soon after, as mesenchymal cells populate the skin to form the underlying collagenous dermis, morphogenesis of the hair follicle begins (Schmidt-Ullrich and Paus, 2005). Specialized dermal cells organize in small clusters directly beneath the epidermal layer, stimulating the overlying epithelial stem cells to grow downward and produce a hair follicle. The follicle is contiguous with the epithelium; both are separated from the dermis by a basement membrane rich in extracellular matrix and growth factors synthesized and deposited largely but not solely by epithelial cells. As the follicle grows down, it assumes the shape of a rod several cell diameters wide. The inner layers begin to differentiate into concentric cylinders to form the central hair shaft (HS) and the surrounding channel, the inner root sheath (IRS). An inductive mesenchymal cluster called the dermal papilla (DP) becomes a permanent part of the follicle base (Jahoda et al., 1984; Kishimoto et al., 2000). It travels with the epithelial downgrowth and becomes enveloped by the hair bulb. The follicle becomes fully mature as its bulb nears the bottom of the dermis. At this point (in mouse back skin around postnatal day 6 or P6), the proliferative cells (matrix) at the follicle base continue to divide, producing progeny cells that terminally differentiate to form the growing hair that exits the skin surface.

Anagen

Histologically, anagen follicles are long and very straight, but the follicles are angled to permit the hair coat to lie flat along the body surface. The proliferating matrix cells have a cell-cycle length of approximately 18 hours (Lavker et al., 2003). Daughter cells move upwards, adopting one of six lineages of the IRS and HS; from outermost to innermost, the layers include Henley, Huxley and cuticle layers of the IRS, and the cuticle, cortex and medulla layers of the HS. As HS cells terminally differentiate, they extrude their organelles and become tightly packed with bundles of 10-nm filaments assembled from cysteine-rich hair keratins, which become physically cross-linked to give the hair shaft high tensile strength and flexibility. The IRS also keratinizes so that it can rigidly support and guide the hair shaft during its differentiation process, but its dead cells degenerate as they reach the upper follicle, thereby releasing the HS that continues through the skin surface. The duration of anagen determines the length of the hair and is dependent upon continued proliferation and differentiation of matrix cells at the follicle base.

Anagen-to-catagen transition

The matrix cells are referred to as transit-amplifying cells because they undergo a limited number of cell divisions before differentiating. As the supply of matrix cells declines, HS and IRS differentiation slow and the follicle enters a destructive phase called catagen. The timing of the first catagen onset varies slightly between strains of mice and varies significantly from one skin region to another. In pigmented mice, the progression of catagen is evident from the color of the skin, which changes from the dark gray to black of anagen to pale pink by telogen. As with morphogenesis, the first catagen begins in a wave, spreading from the top of the head caudally towards the tail and laterally down the sides of the animal. In back skin taken from the midline, the onset of the first catagen ranges from P14 at the upper back near the head to P18 in the lower back near the tail. Catagen lasts 3-4 days in mice.

Some molecular regulators of the anagen-catagen transition have been identified, although how they work together to promote catagen or terminate anagen is not yet understood. Molecules that promote the transition to catagen include the growth factors FGF5 and EGF, neurotrophins such as BDNF and possibly the p75-neurotrophin receptor, p53 and TGFβ-family pathway members such as TGFβ1 and the BMPRIa (Andl et al., 2004; Foitzik et al., 2000; Hansen et al., 1997; Hebert et al., 1994; Schmidt-Ullrich and Paus, 2005). Factors known to maintain anagen include SGK3 and Msx2 (Alonso et al., 2005; Ma et al., 2003).

Catagen

Catagen is the dynamic transition between anagen and telogen (Muller-Rover et al., 2001). During catagen, the lower `cycling' portion of each hair follicle regresses entirely in a process that includes apoptosis of epithelial cells in the bulb and outer root sheath (ORS), the outermost epithelial layer (Lindner et al., 1997). HS differentiation ceases, and the bottom of the HS seals off into a rounded structure called a club, which moves upward until it reaches the permanent, non-cycling upper follicle, where it remains anchored during telogen. As the lower follicle recedes, a temporary structure forms – the epithelial strand – which is unique to catagen. This connects the DP to the upper part of the hair follicle, contains many apoptotic cells and is completely eliminated by the time the DP reaches the cells that surround the remnant club hair.

Telogen

Following catagen, follicles lie dormant in a resting phase (telogen). In mice, the first telogen is short, lasting only 1 or 2 days, from approximately P19 to P21 in the mid back. The second telogen, however, lasts more than 2 weeks, beginning around P42.

The follicle stem cell compartment

Although no new hair follicles are made postnatally, the lower portion of the hair follicle regenerates in order to produce a new hair. For this purpose, and for the maintenance of the epidermis and sebaceous gland, reservoirs of multipotent epithelial stem cells are set aside during development. These precious cells are found in the lowest permanent portion of the hair follicle – the `bulge' (Oshima et al., 2001; Taylor et al., 2000). Follicle stem cells are activated at the telogen-to-anagen transition, to initiate a new round of hair growth.

Telogen-to-anagen transition

The transition from telogen to anagen occurs when one or two quiescent stem cells at the base of the telogen follicle, near the DP, are activated to produce a new hair shaft (Blanpain et al., 2004; Tumbar et al., 2004). These cells now begin to proliferate rapidly, and become the transit-amplifying daughter cells that are fated to form the new hair follicle. The new follicle forms adjacent to the old pocket that harbors the club hair, which will eventually be shed (exogen). This creates the `bulge' and adds a layer to the stem cell reservoir. The new hair emerges from the same upper orifice as the old hair. In many ways, the telogen-to-anagen transition resembles the activation of embryonic skin stem cells that are stimulated to make the follicle de novo. Signaling by Wnts (Gat et al., 1998; Huelsken et al., 2001; Lo Celso et al., 2004; Lowry et al., 2005; Van Mater et al., 2003) and Shh (Callahan et al., 2004; Mill et al., 2003; St-Jacques et al., 1998) is indispensable for new anagen, whereas Bmps (Botchkarev et al., 1999; Kulessa et al., 2000) have been implicated in follicle differentiation. The molecular steps involved are likely to hold clues to understanding the activation and specification of stem cells.

  • © The Company of Biologists Limited 2006

References

  1. ↵
    Alonso, L., Okada, H., Pasolli, H. A., Wakeham, A., You-Ten, A. I., Mak, T. W. and Fuchs, E. (2005). Sgk3 links growth factor signaling to maintenance of progenitor cells in the hair follicle. J. Cell Biol. 170, 559-570.
    OpenUrlAbstract/FREE Full Text
  2. ↵
    Andl, T., Ahn, K., Kairo, A., Chu, E. Y., Wine-Lee, L., Reddy, S. T., Croft, N. J., Cebra-Thomas, J. A., Metzger, D., Chambon, P. et al. (2004). Epithelial Bmpr1a regulates differentiation and proliferation in postnatal hair follicles and is essential for tooth development. Development 131, 2257-2268.
    OpenUrlAbstract/FREE Full Text
  3. ↵
    Blanpain, C., Lowry, W. E., Geoghegan, A., Polak, L. and Fuchs, E. (2004). Self-renewal, multipotency, and the existence of two cell populations within an epithelial stem cell niche. Cell 118, 635-648.
    OpenUrlCrossRefPubMedWeb of Science
  4. ↵
    Botchkarev, V. A., Botchkareva, N. V., Roth, W., Nakamura, M., Chen, L. H., Herzog, W., Lindner, G., McMahon, J. A., Peters, C., Lauster, R. et al. (1999). Noggin is a mesenchymally derived stimulator of hair-follicle induction. Nat. Cell Biol. 1, 158-164.
    OpenUrlCrossRefPubMedWeb of Science
  5. ↵
    Callahan, C. A., Ofstad, T., Horng, L., Wang, J. K., Zhen, H. H., Coulombe, P. A. and Oro, A. E. (2004). MIM/BEG4, a Sonic hedgehog-responsive gene that potentiates Gli-dependent transcription. Genes Dev. 18, 2724-2729.
    OpenUrlAbstract/FREE Full Text
  6. ↵
    Foitzik, K., Lindner, G., Mueller-Roever, S., Maurer, M., Botchkareva, N., Botchkarev, V., Handjiski, B., Metz, M., Hibino, T., Soma, T. et al. (2000). Control of murine hair follicle regression (catagen) by TGF-beta1 in vivo. FASEB J. 14, 752-760.
    OpenUrlAbstract/FREE Full Text
  7. ↵
    Gat, U., DasGupta, R., Degenstein, L. and Fuchs, E. (1998). De Novo hair follicle morphogenesis and hair tumors in mice expressing a truncated beta-catenin in skin. Cell 95, 605-614.
    OpenUrlCrossRefPubMedWeb of Science
  8. ↵
    Hansen, L. A., Alexander, N., Hogan, M. E., Sundberg, J. P., Dlugosz, A., Threadgill, D. W., Magnuson, T. and Yuspa, S. H. (1997). Genetically null mice reveal a central role for epidermal growth factor receptor in the differentiation of the hair follicle and normal hair development. Am. J. Pathol. 150, 1959-1975.
    OpenUrlPubMedWeb of Science
  9. ↵
    Hebert, J. M., Rosenquist, T., Gotz, J. and Martin, G. R. (1994). FGF5 as a regulator of the hair growth cycle: evidence from targeted and spontaneous mutations. Cell 78, 1017-1025.
    OpenUrlCrossRefPubMedWeb of Science
  10. ↵
    Huelsken, J., Vogel, R., Erdmann, B., Cotsarelis, G. and Birchmeier, W. (2001). beta-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin. Cell 105, 533-545.
    OpenUrlCrossRefPubMedWeb of Science
  11. ↵
    Jahoda, C. A., Horne, K. A. and Oliver, R. F. (1984). Induction of hair growth by implantation of cultured dermal papilla cells. Nature 311, 560-562.
    OpenUrlCrossRefPubMedWeb of Science
  12. ↵
    Kishimoto, J., Burgeson, R. E. and Morgan, B. A. (2000). Wnt signaling maintains the hair-inducing activity of the dermal papilla. Genes Dev. 14, 1181-1185.
    OpenUrlAbstract/FREE Full Text
  13. ↵
    Kulessa, H., Turk, G. and Hogan, B. L. (2000). Inhibition of Bmp signaling affects growth and differentiation in the anagen hair follicle. EMBO J. 19, 6664-6674.
    OpenUrlAbstract
  14. ↵
    Lavker, R. M., Sun, T. T., Oshima, H., Barrandon, Y., Akiyama, M., Ferraris, C., Chevalier, G., Favier, B., Jahoda, C. A., Dhouailly, D. et al. (2003). Hair follicle stem cells. J. Invest. Dermatol. Symp. Proc. 8, 28-38.
    OpenUrlCrossRef
  15. ↵
    Lindner, G., Botchkarev, V. A., Botchkareva, N. V., Ling, G., van der Veen, C. and Paus, R. (1997). Analysis of apoptosis during hair follicle regression (catagen). Am. J. Pathol. 151, 1601-1617.
    OpenUrlPubMedWeb of Science
  16. ↵
    Lo Celso, C., Prowse, D. M. and Watt, F. M. (2004). Transient activation of beta-catenin signalling in adult mouse epidermis is sufficient to induce new hair follicles but continuous activation is required to maintain hair follicle tumours. Development 131, 1787-1799.
    OpenUrlAbstract/FREE Full Text
  17. ↵
    Lowry, W. E., Blanpain, C., Nowak, J. A., Guasch, G., Lewis, L. and Fuchs, E. (2005). Defining the impact of beta-catenin/Tcf transactivation on epithelial stem cells. Genes Dev. 19, 1596-1611.
    OpenUrlAbstract/FREE Full Text
  18. ↵
    Ma, L., Liu, J., Wu, T., Plikus, M., Jiang, T. X., Bi, Q., Liu, Y. H., Muller-Rover, S., Peters, H., Sundberg, J. P. et al. (2003). `Cyclic alopecia' in Msx2 mutants: defects in hair cycling and hair shaft differentiation. Development 130, 379-389.
    OpenUrlAbstract/FREE Full Text
  19. ↵
    Mill, P., Mo, R., Fu, H., Grachtchouk, M., Kim, P. C., Dlugosz, A. A. and Hui, C. C. (2003). Sonic hedgehog-dependent activation of Gli2 is essential for embryonic hair follicle development. Genes Dev. 17, 282-294.
    OpenUrlAbstract/FREE Full Text
  20. ↵
    Millar, S. E. (2002). Molecular mechanisms regulating hair follicle development. J. Invest. Dermatol. 118, 216-225.
    OpenUrlCrossRefPubMedWeb of Science
  21. ↵
    Muller-Rover, S., Handjiski, B., van der Veen, C., Eichmuller, S., Foitzik, K., McKay, I. A., Stenn, K. S. and Paus, R. (2001). A comprehensive guide for the accurate classification of murine hair follicles in distinct hair cycle stages. J. Invest. Dermatol. 117, 3-15.
    OpenUrlCrossRefPubMedWeb of Science
  22. ↵
    Oshima, H., Rochat, A., Kedzia, C., Kobayashi, K. and Barrandon, Y. (2001). Morphogenesis and renewal of hair follicles from adult multipotent stem cells. Cell 104, 233-245.
    OpenUrlCrossRefPubMedWeb of Science
  23. ↵
    Schmidt-Ullrich, R. and Paus, R. (2005). Molecular principles of hair follicle induction and morphogenesis. BioEssays 27, 247-261.
    OpenUrlCrossRefPubMedWeb of Science
  24. ↵
    St-Jacques, B., Dassule, H. R., Karavanova, I., Botchkarev, V. A., Li, J., Danielian, P. S., McMahon, J. A., Lewis, P. M., Paus, R. and McMahon, A. P. (1998). Sonic hedgehog signaling is essential for hair development. Curr. Biol. 8, 1058-1068.
    OpenUrlCrossRefPubMedWeb of Science
  25. ↵
    Taylor, G., Lehrer, M. S., Jensen, P. J., Sun, T. T. and Lavker, R. M. (2000). Involvement of follicular stem cells in forming not only the follicle but also the epidermis. Cell 102, 451-461.
    OpenUrlCrossRefPubMedWeb of Science
  26. ↵
    Tumbar, T., Guasch, G., Greco, V., Blanpain, C., Lowry, W. E., Rendl, M. and Fuchs, E. (2004). Defining the epithelial stem cell niche in skin. Science 303, 359-363.
    OpenUrlAbstract/FREE Full Text
  27. ↵
    Van Mater, D., Kolligs, F. T., Dlugosz, A. A. and Fearon, E. R. (2003). Transient activation of beta-catenin signaling in cutaneous keratinocytes is sufficient to trigger the active growth phase of the hair cycle in mice. Genes Dev. 17, 1219-1224.
    OpenUrlAbstract/FREE Full Text
Previous ArticleNext Article
Back to top
Previous ArticleNext Article

This Issue

 Download PDF

Email

Thank you for your interest in spreading the word on Journal of Cell Science.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
The hair cycle
(Your Name) has sent you a message from Journal of Cell Science
(Your Name) thought you would like to see the Journal of Cell Science web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Cell Science at a Glance
The hair cycle
Laura Alonso, Elaine Fuchs
Journal of Cell Science 2006 119: 391-393; doi: 10.1242/jcs.02793
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Cell Science at a Glance
The hair cycle
Laura Alonso, Elaine Fuchs
Journal of Cell Science 2006 119: 391-393; doi: 10.1242/jcs.02793

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Alerts

Please log in to add an alert for this article.

Sign in to email alerts with your email address

Article navigation

  • Top
  • Article
    • Morphogenesis
    • Anagen
    • Anagen-to-catagen transition
    • Catagen
    • Telogen
    • The follicle stem cell compartment
    • Telogen-to-anagen transition
    • References
  • Figures & tables
  • Info & metrics
  • PDF

Related articles

Cited by...

More in this TOC section

  • Cargo transport through the nuclear pore complex at a glance
  • Translation initiation in cancer at a glance
  • Tumour-directed microenvironment remodelling at a glance
Show more CELL SCIENCE AT A GLANCE

Similar articles

Other journals from The Company of Biologists

Development

Journal of Experimental Biology

Disease Models & Mechanisms

Biology Open

Advertisement

2020 at The Company of Biologists

Despite the challenges of 2020, we were able to bring a number of long-term projects and new ventures to fruition. While we look forward to a new year, join us as we reflect on the triumphs of the last 12 months.


Mole – The Corona Files

"This is not going to go away, 'like a miracle.' We have to do magic. And I know we can."

Mole continues to offer his wise words to researchers on how to manage during the COVID-19 pandemic.


Cell scientist to watch – Christine Faulkner

In an interview, Christine Faulkner talks about where her interest in plant science began, how she found the transition between Australia and the UK, and shares her thoughts on virtual conferences.


Read & Publish participation extends worldwide

“The clear advantages are rapid and efficient exposure and easy access to my article around the world. I believe it is great to have this publishing option in fast-growing fields in biomedical research.”

Dr Jaceques Behmoaras (Imperial College London) shares his experience of publishing Open Access as part of our growing Read & Publish initiative. We now have over 60 institutions in 12 countries taking part – find out more and view our full list of participating institutions.


JCS and COVID-19

For more information on measures Journal of Cell Science is taking to support the community during the COVID-19 pandemic, please see here.

If you have any questions or concerns, please do not hestiate to contact the Editorial Office.

Articles

  • Accepted manuscripts
  • Issue in progress
  • Latest complete issue
  • Issue archive
  • Archive by article type
  • Special issues
  • Subject collections
  • Interviews
  • Sign up for alerts

About us

  • About Journal of Cell Science
  • Editors and Board
  • Editor biographies
  • Travelling Fellowships
  • Grants and funding
  • Journal Meetings
  • Workshops
  • The Company of Biologists

For Authors

  • Submit a manuscript
  • Aims and scope
  • Presubmission enquiries
  • Fast-track manuscripts
  • Article types
  • Manuscript preparation
  • Cover suggestions
  • Editorial process
  • Promoting your paper
  • Open Access
  • JCS Prize
  • Manuscript transfer network
  • Biology Open transfer

Journal Info

  • Journal policies
  • Rights and permissions
  • Media policies
  • Reviewer guide
  • Sign up for alerts

Contacts

  • Contact JCS
  • Subscriptions
  • Advertising
  • Feedback

Twitter   YouTube   LinkedIn

© 2021   The Company of Biologists Ltd   Registered Charity 277992