A comprehensive guide for the recognition and classification of distinct stages of hair follicle morphogenesis
Open accessAbstract
Numerous spontaneous and experimentally induced mouse mutations develop a hair phenotype, which is often associated with more or less discrete abnormalities in hair follicle development. In order to recognize these, it is critically important to be able to determine and to classify accurately the major stages of normal murine hair follicle morphogenesis. As an aid, we propose a pragmatic and comprehensive guide, modified after previous suggestions by Hardy, and provide a list of easily recognizable classification criteria, illustrated by representative micrographs. Basic and more advanced criteria are distinguished, the former being applicable to all mouse strains and requiring only simple histologic stains (hematoxylin and eosin, Giemsa, periodic acid Schiff, alkaline phosphatase activity), the latter serving as auxiliary criteria, which require a pigmented mouse strain (like C57BL/6J) or immunohistochemistry (interleukin-1 receptor type I, transforming growth factor-beta receptor type II). In addition, we present simplified, computer-generated schematic drawings for the standardized recording and reporting of gene and antigen expression patterns during hair follicle development. This classification aid serves as a basic introduction into the field of hair follicle morphogenesis, aims at standardizing the presentation of related hair research data, and should become a useful tool when screening new mouse mutants for discrete abnormalities of hair follicle morphogenesis (compared with the respective wild type) in a highly reproducible, easily applicable, and quantifiable manner.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
During embryonic stages 7-8, neural crest-derived melanocytes in the HF matrix pigment the hair shaft, sebaceous glands and arrector pili muscles develop, and the dermis forms a hypodermal layer rich with adipocytes.
“During the embryonic stages 7–8, neural crest-derived melanocytes in the HF matrix pigment the hair shaft, sebaceous glands (SGs) and arrector pili muscles develop, and the dermis forms a hypodermal layer rich with adipocytes (Paus et al., 1999).”
From Hair Follicle Development in Mouse Pluripotent Stem Cell-Derived Skin Organoids (2018) · cites this paper as Paus et al., 1999
The Stage 7 section describes the hair shaft entering the canal beside an enlarged sebaceous gland, and Stage 8 describes a prominent shaft emerging through the epidermis. Stages 5–6 place the onset of pigmentation and sebaceous-gland formation earlier than stages 7–8. Our copy does not establish the melanocytes’ neural-crest origin, development of arrector pili muscles at these stages, or formation of an adipocyte-rich hypodermal layer; the Stage 8 subcutaneous muscle layer is not identified as the arrector pili muscle. No page numbers are available in the indexed passages. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn mice, HF development has been classified into discrete stages.
“In mice, HF development has been classified into discrete stages (Paus et al., 1999; Figure 4A).”
From Hair Follicle Development in Mouse Pluripotent Stem Cell-Derived Skin Organoids (2018) · cites this paper as Paus et al., 1999
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Cotsarelis, G., Sun, T.-T., & Lavker, R. M. (1990) · Cell · doi:10.1016/0092-8674(90)90696-c · Cited by 2,276 · see citing works
E‐ and P‐cadherin expression during murine hair follicle morphogenesis and cycling
Müller‐Röver, S., Tokura, Y., Welker, P., Furukawa, F., Wakita, H., Takigawa, M., & Paus, R. (1999) · Experimental Dermatology · doi:10.1111/j.1600-0625.1999.tb00377.x · Cited by 86 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 10
- Abell E: Embryology and anatomy of the hair follicle. In: Olsen EA (ed.). Disorders of Hair Growth, New York: McGraw Hill, 1994, pp. 1-20
- Montagna W, van Scott EJ: The anatomy of the hair follicle. In: Montagna W, Ellis RA (eds). The Biology of the Hair Growth. New York: Academic Press, 1958
- Mu ¨ller-Ro ¨ver S, Paus R. Topobiology of the hair follicle: adhesion molecules as morphoregulatory signals during hair follicle morphogenesis. In: Chuong CM (ed.). Molecular Basis of Epithelial Appendage Morphogenesis. Austin, TX: Landes Bioscience Publishers, 1998, pp 283-314
- Panteleyev AA, van der Veen C, Rosenbach T, Mu ¨ller-Ro ¨ver S, Sokolov VE, Paus R: Towards defining the pathogenesis of the hairless phenotype. J Invest Dermatol 110(6):902-907, 1998
- Philpott MP, Paus R. Principles of hair follicle morphogenesis. In: Chuong CM (ed.) Molecular Basis of Epithelial Appendage Morphogenesis. Austin, TX: Landes Bioscience Publishers, 1998, pp 75-103
- Pinkus F: The development of the integument. In: Kabel G, Mall S (eds). Manual of Human Embryology. Philadelphia: Lippincott, 1910, pp 243-291
- Pinkus H: Embryology of hair. In: Montagna W, Ellis RA (eds). The Biology of the Hair Growth. New York: Academic Press, 1958, pp 1-32
- Stenn K, Parimoo S, Prouty S: Growth of the hair follicle: A cycling and regenerating biological system. In: Chuong CM (ed.). Molecular Basis of Epithelial Appendage Morphogenesis. Austin, TX: Landes Bioscience Publishers, 1998, pp 111-124
- Sundberg JP: Handbook of Mouse Mutations with Skin and Hair Abnormalities. Boca Raton: CRC Press, 1994
- Sundberg JP, Hogan ME: Hair types and subtypes in the mouse. In: Handbook of Mouse Mutations with Skin and Hair Abnormalities. Boca Raton: CRC Press, 1994, pp 57-68
Cited by
Sorted by citations
Melanocyte biology and skin pigmentation
Lin, J. Y., & Fisher, D. E. (2007) · Nature · doi:10.1038/nature05660 · Cited by 1,379 · see citing works
Müller-Röver, S., Foitzik, K., Paus, R., Handjiski, B., van der Veen, C., Eichmüller, S., McKay, I. A., & Stenn, K. S. (2001) · Journal of Investigative Dermatology · doi:10.1046/j.0022-202x.2001.01377.x · Cited by 1,375 · see citing works
Self-citationMechanisms of hair graying: incomplete melanocyte stem cell maintenance in the niche
Nishimura, E. K., Granter, S. R., & Fisher, D. E. (2005) · Science · doi:10.1126/science.1099593 · Cited by 750 · see citing works
Msx2 deficiency in mice causes pleiotropic defects in bone growth and ectodermal organ formation
Satokata, I., Ma, L., Ohshima, H., Bei, M., Woo, I., Nishizawa, K., Maeda, T., Takano, Y., Uchiyama, M., Heaney, S., et al. (2000) · Nature Genetics · doi:10.1038/74231 · Cited by 737 · see citing works
A wave of regulatory T cells into neonatal skin mediates tolerance to commensal microbes
Scharschmidt, T. C., Vasquez, K. S., Truong, H.-A., Gearty, S. V., Pauli, M. L., Nosbaum, A., Gratz, I. K., Otto, M., Moon, J. J., Liese, J., et al. (2015) · Immunity · doi:10.1016/j.immuni.2015.10.016 · Cited by 586 · see citing works
Review of hair follicle dermal cells
Yang, C.-C., & Cotsarelis, G. (2010) · Journal of Dermatological Science · doi:10.1016/j.jdermsci.2009.11.005 · Cited by 418 · see citing works
mTOR mediates Wnt-induced epidermal stem cell exhaustion and aging
Castilho, R. M., Squarize, C. H., Chodosh, L. A., Williams, B. O., & Gutkind, J. S. (2009) · Cell stem cell · doi:10.1016/j.stem.2009.06.017 · Cited by 371 · see citing works
Sox2-positive dermal papilla cells specify hair follicle type in mammalian epidermis
Driskell, R. R., Giangreco, A., Jensen, K. B., Mulder, K. W., & Watt, F. M. (2009) · Development · doi:10.1242/dev.038620 · Cited by 331 · see citing works
Chen, D., Jarrell, A., Guo, C., Lang, R., & Atit, R. (2012) · Development · doi:10.1242/dev.076463 · Cited by 260 · see citing works
Scharschmidt, T. C., Vasquez, K. S., Pauli, M. L., Leitner, E. G., Chu, K., Truong, H.-A., Lowe, M. M., Sanchez Rodriguez, R., Ali, N., Laszik, Z. G., et al. (2017) · Cell Host & Microbe · doi:10.1016/j.chom.2017.03.001 · Cited by 258 · see citing works
Hair Follicle Development in Mouse Pluripotent Stem Cell-Derived Skin Organoids
Lee, J., Bӧscke, R., Tang, P.-C., Hartman, B. H., Heller, S., & Koehler, K. R. (2018) · Cell Reports · doi:10.1016/j.celrep.2017.12.007 · Cited by 187 · see citing works
E‐cadherin controls adherens junctions in the epidermis and the renewal of hair follicles
Young, P., Boussadia, O., Halfter, H., Grose, R., Berger, P., Leone, D. P., Robenek, H., Charnay, P., Kemler, R., & Suter, U. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg560 · Cited by 156 · see citing works
Kindlin-1 controls Wnt and TGF-β availability to regulate cutaneous stem cell proliferation
Rognoni, E., Widmaier, M., Jakobson, M., Ruppert, R., Ussar, S., Katsougkri, D., Böttcher, R. T., Lai-Cheong, J. E., Rifkin, D. B., McGrath, J. A., et al. (2014) · Nature Medicine · doi:10.1038/nm.3490 · Cited by 140 · see citing works
Epidermal Development in Mammals: Key Regulators, Signals from Beneath, and Stem Cells
Liu, S., Zhang, H., & Duan, E. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms140610869 · Cited by 110 · see citing works
A Clinical and Biological Guide for Understanding Chemotherapy-Induced Alopecia and Its Prevention
Dunnill, C. J., Al-Tameemi, W., Collett, A., Haslam, I. S., & Georgopoulos, N. T. (2018) · The Oncologist · doi:10.1634/theoncologist.2017-0263 · Cited by 96 · see citing works
Jenkins, B. A., & Lumpkin, E. A. (2017) · Development · doi:10.1242/dev.120402 · Cited by 79 · see citing works
Human reconstructed skin xenografts on mice to model skin physiology
Salgado, G., Ng, Y. Z., Koh, L. F., Goh, C. S. M., & Common, J. E. (2017) · Differentiation · doi:10.1016/j.diff.2017.09.004 · Cited by 56 · see citing works
Ras signaling is essential for skin development
Drosten, M., Lechuga, C. G., & Barbacid, M. (2014) · Oncogene · doi:10.1038/onc.2013.254 · Cited by 46 · see citing works
Maier, H., Meixner, M., Hartmann, D., Sandhoff, R., Wang-Eckhardt, L., Zöller, I., Gieselmann, V., & Eckhardt, M. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.231977 · Cited by 45 · see citing works
Genetic variation of the cutaneous HPA axis: an analysis of UVB-induced differential responses
Skobowiat, C., Nejati, R., Lu, L., Williams, R. W., & Slominski, A. T. (2013) · Gene · doi:10.1016/j.gene.2013.08.035 · Cited by 42 · see citing works
Song, P. H., Park, G.-R., Kim, Y.-H., Jung, D. H., Ku, S.-K., & Song, C.-H. (2021) · Applied Sciences · doi:10.3390/app11031195 · Cited by 9 · see citing works
- Authors
- van der Veen, C., Handjiski, B., Paus, R., Müller-Röver, S., Maurer, M., Eichmüller, S., Ling, G., Hofmann, U., Foitzik, K., & Mecklenburg, L.
- Affiliations
- Humboldt-Universität zu Berlin (DE)
- Beth Israel Deaconess Medical Center (US)
- German Cancer Research Center (DE)
- Universität Hamburg (DE)
- Corresponding author
- Paus, Ralf
- Venue
- Journal of Investigative Dermatology
- Publisher
- Elsevier BV
- Published
- 1999-10
- Volume
- 113
- Issue
- 4
- Pages
- 523-532
- ISSN
- 0022-202X (ISSN-L)
- OpenAlex
- W2041693867
- Cited by
- 553
- References
- 2
- Citations by year
- 2026: 11 · 2025: 12 · 2024: 22 · 2023: 16 · 2022: 21 · 2021: 18 · 2020: 23 · 2019: 23 · 2018: 18 · 2017: 27 · 2016: 25 · 2015: 21 · 2014: 28 · 2013: 27 · 2012: 32
- FWCI
- 20.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Investigative Dermatology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Urology › Hair Growth and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › dental development and anomalies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Keywords
- hair follicle morphogenesis, classification criteria, mouse mutants, tissue staining, IL1R1, gene expression patterns, immunohistochemistry, standardized reporting
- MeSH terms
- Receptor, Transforming Growth Factor-beta Type II, Animals, Immunohistochemistry, Mice, Inbred C57BL, Mice, Transgenic, Morphogenesis, Phenotype, Protein Serine-Threonine Kinases, Receptors, Interleukin-1, Receptors, Transforming Growth Factor beta, Hair Follicle, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review