Scratching the surface of skin development


The epidermis and its appendages develop from a single layer of multipotent embryonic progenitor keratinocytes. Embryonic stem cells receive cues from their environment that instruct them to commit to a particular differentiation programme and generate a stratified epidermis, hair follicles or sebaceous glands. Exciting recent developments have focused on how adult skin epithelia maintain populations of stem cells for use in the natural cycles of hair follicle regeneration and for re-epithelialization in response to wounding.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Early signalling steps in specification of embryonic skin.
Figure 2: Rapidly proliferating matrix-cell progenitors are spatially organized in the hair bulb to respond to distinct differentiation-specific cues.
Figure 3: The hair cycle.
Figure 4: Diagram of the follicle stem-cell niche.
Figure 5: Model for control of epidermal proliferation.
Figure 6: Models of how epidermal homeostasis might be achieved.


  1. 1

    Stern, C. D. Neural induction: old problem, new findings, yet more questions. Development 132, 2007–2021 (2005).

    CAS  PubMed  Google Scholar 

  2. 2

    M'Boneko, V. & Merker, H. J. Development and morphology of the periderm of mouse embryos (days 9–12 of gestation). Acta Anat. (Basel) 133, 325–336 (1988).

    CAS  PubMed  Google Scholar 

  3. 3

    Atit, R. et al. β-catenin activation is necessary and sufficient to specify the dorsal dermal fate in the mouse. Dev. Biol. 296, 164–176 (2006).

    CAS  PubMed  Google Scholar 

  4. 4

    Hardy, M. H. The secret life of the hair follicle. Trends Genet. 8, 55–61 (1992).

    CAS  PubMed  Google Scholar 

  5. 5

    Olivera-Martinez, I., Thelu, J. & Dhouailly, D. Molecular mechanisms controlling dorsal dermis generation from the somitic dermomyotome. Int. J. Dev. Biol. 48, 93–101 (2004).

    CAS  PubMed  Google Scholar 

  6. 6

    Davidson, D. The mechanism of feather pattern development in the chick. II. Control of the sequence of pattern formation. J. Embryol. Exp. Morphol. 74, 261–273 (1983).

    CAS  PubMed  Google Scholar 

  7. 7

    Petiot, A. et al. A crucial role for Fgfr2-IIIb signalling in epidermal development and hair follicle patterning. Development 130, 5493–5501 (2003).

    CAS  Google Scholar 

  8. 8

    Jung, H. S. et al. Local inhibitory action of BMPs and their relationships with activators in feather formation: implications for periodic patterning. Dev. Biol. 196, 11–23 (1998).

    CAS  PubMed  Google Scholar 

  9. 9

    Noramly, S. & Morgan, B. A. BMPs mediate lateral inhibition at successive stages in feather tract development. Development 125, 3775–3787 (1998).

    CAS  PubMed  Google Scholar 

  10. 10

    Botchkarev, V. A. et al. Noggin is a mesenchymally derived stimulator of hair-follicle induction. Nature Cell Biol. 1, 158–164 (1999).

    CAS  PubMed  Google Scholar 

  11. 11

    Mou, C., Jackson, B., Schneider, P., Overbeek, P. A. & Headon, D. J. Generation of the primary hair follicle pattern. Proc. Natl Acad. Sci. USA 103, 9075–9080 (2006).

    ADS  CAS  PubMed  Google Scholar 

  12. 12

    Gat, U., DasGupta, R., Degenstein, L. & Fuchs, E. De novo hair follicle morphogenesis and hair tumors in mice expressing a truncated β-catenin in skin. Cell 95, 605–614 (1998).

    CAS  Google Scholar 

  13. 13

    DasGupta, R. & Fuchs, E. Multiple roles for activated LEF/TCF transcription complexes during hair follicle development and differentiation. Development 126, 4557–4568 (1999).

    CAS  PubMed  Google Scholar 

  14. 14

    Noramly, S., Freeman, A. & Morgan, B. A. β-catenin signaling can initiate feather bud development. Development 126, 3509–3521 (1999).

    CAS  PubMed  Google Scholar 

  15. 15

    St-Jacques, B. et al. Sonic hedgehog signaling is essential for hair development. Curr. Biol. 8, 1058–1068 (1998).

    CAS  PubMed  Google Scholar 

  16. 16

    Oro, A. E. & Higgins, K. Hair cycle regulation of Hedgehog signal reception. Dev. Biol. 255, 238–248 (2003).

    CAS  PubMed  Google Scholar 

  17. 17

    Levy, V., Lindon, C., Harfe, B. D. & Morgan, B. A. Distinct stem cell populations regenerate the follicle and interfollicular epidermis. Dev. Cell 9, 855–861 (2005).

    CAS  PubMed  Google Scholar 

  18. 18

    Reddy, S. et al. Characterization of Wnt gene expression in developing and postnatal hair follicles and identification of Wnt5a as a target of Sonic hedgehog in hair follicle morphogenesis. Mech. Dev. 107, 69–82 (2001).

    CAS  PubMed  Google Scholar 

  19. 19

    Merrill, B. J., Gat, U., DasGupta, R. & Fuchs, E. Tcf3 and Lef1 regulate lineage differentiation of multipotent stem cells in skin. Genes Dev. 15, 1688–1705 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. 20

    Hurlstone, A. & Clevers, H. T-cell factors: turn-ons and turn-offs. EMBO J. 21, 2303–2311 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. 21

    Nguyen, H., Rendl, M. & Fuchs, E. Tcf3 maintains stem cells and represses cell fate determination in skin. Cell 127, 171–183 (2006).

    CAS  PubMed  Google Scholar 

  22. 22

    van Genderen, C. et al. Development of several organs that require inductive epithelial–mesenchymal interactions is impaired in LEF-1-deficient mice. Genes Dev. 8, 2691–2703 (1994).

    CAS  Google Scholar 

  23. 23

    Van Mater, D., Kolligs, F. T., Dlugosz, A. A. & Fearon, E. R. Transient activation of β-catenin signaling in cutaneous keratinocytes is sufficient to trigger the active growth phase of the hair cycle in mice. Genes Dev. 17, 1219–1224 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. 24

    Lo Celso, C., Prowse, D. M. & Watt, F. M. Transient activation of β-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 (2004).

    CAS  PubMed  Google Scholar 

  25. 25

    Lowry, W. E. et al. Defining the impact of β-catenin/Tcf transactivation on epithelial stem cells. Genes Dev. 19, 1596–1611 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. 26

    Huelsken, J., Vogel, R., Erdmann, B., Cotsarelis, G. & Birchmeier, W. β-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin. Cell 105, 533–545 (2001).

    CAS  PubMed  Google Scholar 

  27. 27

    Andl, T., Reddy, S. T., Gaddapara, T. & Millar, S. E. WNT signals are required for the initiation of hair follicle development. Dev. Cell 2, 643–653 (2002).

    CAS  PubMed  Google Scholar 

  28. 28

    Jamora, C., DasGupta, R., Kocieniewski, P. & Fuchs, E. Links between signal transduction, transcription and adhesion in epithelial bud development. Nature 422, 317–322 (2003).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  29. 29

    Kobielak, K., Pasolli, H. A., Alonso, L., Polak, L. & Fuchs, E. Defining BMP functions in the hair follicle by conditional ablation of BMP receptor IA. J. Cell Biol. 163, 609–623 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. 30

    Andl, T. et al. Epithelial Bmpr1a regulates differentiation and proliferation in postnatal hair follicles and is essential for tooth development. Development 131, 2257–2268 (2004).

    CAS  PubMed  Google Scholar 

  31. 31

    Rhee, H., Polak, L. & Fuchs, E. Lhx2 maintains stem cells character in hair follicles. Science 312, 1946–1949 (2006).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  32. 32

    Headon, D. J. et al. Gene defect in ectodermal dysplasia implicates a death domain adapter in development. Nature 414, 913–916 (2001).

    ADS  CAS  PubMed  Google Scholar 

  33. 33

    Schmidt-Ullrich, R. et al. NF-κB transmits Eda A1/EdaR signalling to activate Shh and cyclin D1 expression, and controls post-initiation hair placode down growth. Development 133, 1045–1057 (2006).

    CAS  PubMed  Google Scholar 

  34. 34

    Rinn, J. L., Bondre, C., Gladstone, H. B., Brown, P. O. & Chang, H. Y. Anatomic demarcation by positional variation in fibroblast gene expression programs. PLoS Genet. 2, e119 (2006).

    PubMed  PubMed Central  Google Scholar 

  35. 35

    Atit, R., Conlon, R. A. & Niswander, L. EGF signaling patterns the feather array by promoting the interbud fate. Dev. Cell 4, 231–240 (2003).

    CAS  PubMed  Google Scholar 

  36. 36

    Blanpain, C. & Fuchs, E. Epidermal stem cells of the skin. Annu. Rev. Cell Dev. Biol. 22, 339–373 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. 37

    Muller-Rover, S. et al. A comprehensive guide for the accurate classification of murine hair follicles in distinct hair cycle stages. J. Invest. Dermatol. 117, 3–15 (2001).

    CAS  PubMed  Google Scholar 

  38. 38

    Kopan, R. et al. Genetic mosaic analysis indicates that the bulb region of coat hair follicles contains a resident population of several active multipotent epithelial lineage progenitors. Dev. Biol. 242, 44–57 (2002).

    CAS  PubMed  Google Scholar 

  39. 39

    Legue, E. & Nicolas, J. F. Hair follicle renewal: organization of stem cells in the matrix and the role of stereotyped lineages and behaviors. Development 132, 4143–4154 (2005).

    CAS  PubMed  Google Scholar 

  40. 40

    Lechler, T. & Fuchs, E. Asymmetric cell divisions promote stratification and differentiation of mammalian skin. Nature 437, 275–280 (2005).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  41. 41

    Langbein, L. & Schweizer, J. Keratins of the human hair follicle. Int. Rev. Cytol. 243, 1–78 (2005).

    CAS  PubMed  Google Scholar 

  42. 42

    Chan, E. F., Gat, U., McNiff, J. M. & Fuchs, E. A common human skin tumour is caused by activating mutations in β-catenin. Nature Genet. 21, 410–413 (1999).

    CAS  PubMed  Google Scholar 

  43. 43

    Godwin, A. R. & Capecchi, M. R. Hoxc13 mutant mice lack external hair. Genes Dev. 12, 11–20 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. 44

    Dai, X. & Segre, J. A. Transcriptional control of epidermal specification and differentiation. Curr. Opin. Genet. Dev. 14, 485–491 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. 45

    Ellis, T. et al. The transcriptional repressor CDP (Cutl1) is essential for epithelial cell differentiation of the lung and the hair follicle. Genes Dev. 15, 2307–2319 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. 46

    Kaufman, C. K. et al. GATA-3: an unexpected regulator of cell lineage determination in skin. Genes Dev. 17, 2108–2122 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. 47

    Horsley, V. et al. Blimp1 defines a progenitor population that governs cellular input to the sebaceous gland. Cell 126, 597–609 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. 48

    Ancelin, K. et al. Blimp1 associates with Prmt5 and directs histone arginine methylation in mouse germ cells. Nature Cell Biol. 8, 623–630 (2006).

    CAS  PubMed  Google Scholar 

  49. 49

    Chang, D. H., Angelin-Duclos, C. & Calame, K. BLIMP-1: trigger for differentiation of myeloid lineage. Nature Immunol. 1, 169–176 (2000).

    CAS  Google Scholar 

  50. 50

    De Strooper, B. et al. A presenilin-1-dependent γ-secretase-like protease mediates release of Notch intracellular domain. Nature 398, 518–522 (1999).

    ADS  CAS  PubMed  Google Scholar 

  51. 51

    Pan, Y. et al. γ-Secretase functions through Notch signaling to maintain skin appendages but is not required for their patterning or initial morphogenesis. Dev. Cell 7, 731–743 (2004).

    CAS  PubMed  Google Scholar 

  52. 52

    Blanpain, C., Lowry, W. E., Pasolli, H. A. & Fuchs, E. Canonical Notch signaling functions as a commitment switch in the epidermal lineage. Genes Dev. 20, 3022–3035 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. 53

    Ming Kwan, K., Li, A. G., Wang, X. J., Wurst, W. & Behringer, R. R. Essential roles of BMPR-IA signaling in differentiation and growth of hair follicles and in skin tumorigenesis. Genesis 39, 10–25 (2004).

    PubMed  Google Scholar 

  54. 54

    Schmidt-Ullrich, R. & Paus, R. Molecular principles of hair follicle induction and morphogenesis. BioEssays 27, 247–261 (2005).

    CAS  PubMed  Google Scholar 

  55. 55

    Tong, X. & Coulombe, P. A. Keratin 17 modulates hair follicle cycling in a TNFα-dependent fashion. Genes Dev. 20, 1353–1364 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. 56

    Potter, G. B. et al. The hairless gene mutated in congenital hair loss disorders encodes a novel nuclear receptor corepressor. Genes Dev. 15, 2687–2701 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. 57

    Klose, R. J. et al. The transcriptional repressor JHDM3A demethylates trimethyl histone H3 lysine 9 and lysine 36. Nature 442, 312–316 (2006).

    ADS  CAS  PubMed  Google Scholar 

  58. 58

    Cotsarelis, G., Sun, T. T. & Lavker, R. M. Label-retaining cells reside in the bulge area of pilosebaceous unit: implications for follicular stem cells, hair cycle, and skin carcinogenesis. Cell 61, 1329–1337 (1990).

    CAS  PubMed  Google Scholar 

  59. 59

    Taylor, G., Lehrer, M. S., Jensen, P. J., Sun, T. T. & Lavker, R. M. Involvement of follicular stem cells in forming not only the follicle but also the epidermis. Cell 102, 451–461 (2000).

    CAS  PubMed  Google Scholar 

  60. 60

    Oshima, H., Rochat, A., Kedzia, C., Kobayashi, K. & Barrandon, Y. Morphogenesis and renewal of hair follicles from adult multipotent stem cells. Cell 104, 233–245 (2001).

    CAS  PubMed  Google Scholar 

  61. 61

    Blanpain, C., Lowry, W. E., Geoghegan, A., Polak, L. & Fuchs, E. Self-renewal, multipotency, and the existence of two cell populations within an epithelial stem cell niche. Cell 118, 635–648 (2004).

    CAS  PubMed  Google Scholar 

  62. 62

    Tumbar, T. et al. Defining the epithelial stem cell niche in skin. Science 303, 359–363 (2004).

    ADS  CAS  Google Scholar 

  63. 63

    Morris, R. J. et al. Capturing and profiling adult hair follicle stem cells. Nature Biotechnol. 22, 411–417 (2004).

    CAS  Google Scholar 

  64. 64

    Ohyama, M. et al. Characterization and isolation of stem cell-enriched human hair follicle bulge cells. J. Clin. Invest. 116, 249–260 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. 65

    Claudinot, S., Nicolas, M., Oshima, H., Rochat, A. & Barrandon, Y. Long-term renewal of hair follicles from clonogenic multipotent stem cells. Proc. Natl Acad. Sci. USA 102, 14677–14682 (2005).

    ADS  CAS  PubMed  Google Scholar 

  66. 66

    Arnold, I. & Watt, F. M. c-Myc activation in transgenic mouse epidermis results in mobilization of stem cells and differentiation of their progeny. Curr. Biol. 11, 558–568 (2001).

    CAS  PubMed  Google Scholar 

  67. 67

    Waikel, R. L., Kawachi, Y., Waikel, P. A., Wang, X. J. & Roop, D. R. Deregulated expression of c-Myc depletes epidermal stem cells. Nature Genet. 28, 165–168 (2001).

    CAS  PubMed  Google Scholar 

  68. 68

    Zanet, J. et al. Endogenous Myc controls mammalian epidermal cell size, hyperproliferation, endoreplication and stem cell amplification. J. Cell Sci. 118, 1693–1704 (2005).

    CAS  PubMed  Google Scholar 

  69. 69

    Benitah, S. A., Frye, M., Glogauer, M. & Watt, F. M. Stem cell depletion through epidermal deletion of Rac1. Science 309, 933–935 (2005).

    ADS  PubMed  Google Scholar 

  70. 70

    Wu, X. et al. Cdc42 controls progenitor cell differentiation and β-catenin turnover in skin. Genes Dev. 20, 571–585 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. 71

    Niemann, C., Owens, D. M., Hulsken, J., Birchmeier, W. & Watt, F. M. Expression of ΔNLef1 in mouse epidermis results in differentiation of hair follicles into squamous epidermal cysts and formation of skin tumours. Development 129, 95–109 (2002).

    CAS  PubMed  Google Scholar 

  72. 72

    Takeda, H. et al. Human sebaceous tumors harbor inactivating mutations in LEF1. Nature Med. 12, 395–397 (2006).

    CAS  PubMed  Google Scholar 

  73. 73

    Ghazizadeh, S. & Taichman, L. B. Multiple classes of stem cells in cutaneous epithelium: a lineage analysis of adult mouse skin. EMBO J. 20, 1215–1222 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. 74

    Panteleyev, A. A., Paus, R. & Christiano, A. M. Patterns of hairless (hr) gene expression in mouse hair follicle morphogenesis and cycling. Am. J. Pathol. 157, 1071–1079 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. 75

    Fuchs, E. & Green, H. Changes in keratin gene expression during terminal differentiation of the keratinocyte. Cell 19, 1033–1042 (1980).

    CAS  PubMed  Google Scholar 

  76. 76

    Coulombe, P. A. & Wong, P. Cytoplasmic intermediate filaments revealed as dynamic and multipurpose scaffolds. Nature Cell Biol. 6, 699–706 (2004).

    CAS  PubMed  Google Scholar 

  77. 77

    Kim, S., Wong, P. & Coulombe, P. A. A keratin cytoskeletal protein regulates protein synthesis and epithelial cell growth. Nature 441, 362–365 (2006).

    ADS  CAS  PubMed  Google Scholar 

  78. 78

    Watt, F. M. Role of integrins in regulating epidermal adhesion, growth and differentiation. EMBO J. 21, 3919–3926 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. 79

    Wilhelmsen, K., Litjens, S. H. & Sonnenberg, A. Multiple functions of the integrin α6β4 in epidermal homeostasis and tumorigenesis. Mol. Cell Biol. 26, 2877–2886 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  80. 80

    Raghavan, S., Vaezi, A. & Fuchs, E. A role for αβ1 integrins in focal adhesion function and polarized cytoskeletal dynamics. Dev. Cell 5, 415–427 (2003).

    CAS  PubMed  Google Scholar 

  81. 81

    Brakebusch, C. & Fassler, R. β 1 integrin function in vivo: adhesion, migration and more. Cancer Metastasis Rev. 24, 403–411 (2005).

    CAS  PubMed  Google Scholar 

  82. 82

    Perez-Moreno, M. & Fuchs, E. Catenins: keeping cells from getting their signals crossed. Dev. Cell 11, 601–612 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. 83

    van Roy, F. M. & McCrea, P. D. A role for Kaiso-p120ctn complexes in cancer? Nature Rev. Cancer 5, 956–964 (2005).

    CAS  Google Scholar 

  84. 84

    Perez-Moreno, M. et al. p120-catenin mediates inflammatory responses in the skin. Cell 124, 631–644 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. 85

    Kobielak, A. & Fuchs, E. Links between α-catenin, NF-κB, and squamous cell carcinoma in skin. Proc. Natl Acad. Sci. USA 103, 2322–2327 (2006).

    ADS  CAS  PubMed  Google Scholar 

  86. 86

    Zenz, R. et al. Psoriasis-like skin disease and arthritis caused by inducible epidermal deletion of Jun proteins. Nature 437, 369–375 (2005).

    ADS  CAS  Google Scholar 

  87. 87

    Zhang, J. Y., Green, C. L., Tao, S. & Khavari, P. A. NF-κB RelA opposes epidermal proliferation driven by TNFR1 and JNK. Genes Dev. 18, 17–22 (2004).

    PubMed  PubMed Central  Google Scholar 

  88. 88

    Vasioukhin, V., Bauer, C., Degenstein, L., Wise, B. & Fuchs, E. Hyperproliferation and defects in epithelial polarity upon conditional ablation of α-catenin in skin. Cell 104, 605–617 (2001).

    CAS  PubMed  Google Scholar 

  89. 89

    Zhang, W. et al. E-cadherin loss promotes the initiation of squamous cell carcinoma invasion through modulation of integrin-mediated adhesion. J. Cell Sci. 119, 283–291 (2006).

    CAS  PubMed  Google Scholar 

  90. 90

    Kolodka, T. M., Garlick, J. A. & Taichman, L. B. Evidence for keratinocyte stem cells in vitro: long term engraftment and persistence of transgene expression from retrovirus-transduced keratinocytes. Proc. Natl Acad. Sci. USA 95, 4356–4361 (1998).

    ADS  CAS  PubMed  Google Scholar 

  91. 91

    Ito, M. et al. Stem cells in the hair follicle bulge contribute to wound repair but not to homeostasis of the epidermis. Nature Med. 11, 1351–1354 (2005).

    CAS  PubMed  Google Scholar 

  92. 92

    Mackenzie, I. C. Relationship between mitosis and the ordered structure of the stratum corneum in mouse epidermis. Nature 226, 653–655 (1970).

    ADS  CAS  PubMed  Google Scholar 

  93. 93

    Potten, C. S. Cell replacement in epidermis (keratopoiesis) via discrete units of proliferation. Int. Rev. Cytol. 69, 271–318 (1981).

    CAS  PubMed  Google Scholar 

  94. 94

    Smart, I. H. Variation in the plane of cell cleavage during the process of stratification in the mouse epidermis. Br. J. Dermatol. 82, 276–282 (1970).

    CAS  PubMed  Google Scholar 

  95. 95

    Mills, A. A. et al. p63 is a p53 homologue required for limb and epidermal morphogenesis. Nature 398, 708–713 (1999).

    ADS  CAS  PubMed  Google Scholar 

  96. 96

    Yang, A. et al. p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development. Nature 398, 714–718 (1999).

    ADS  CAS  Google Scholar 

  97. 97

    Hu, Y. et al. IKKα controls formation of the epidermis independently of NF-κB. Nature 410, 710–714 (2001).

    ADS  CAS  PubMed  Google Scholar 

  98. 98

    Green, H. Cultured cells for the treatment of disease. Sci. Am. 265, 96–102 (1991).

    ADS  CAS  PubMed  Google Scholar 

  99. 99

    Li, J., Greco, V., Guasch, G., Fuchs, E. & Mombaerts, P. Mice cloned from adult skin cells. Proc. Natl Acad. Sci. USA (in the press).

  100. 100

    Paus, R. & Cotsarelis, G. The biology of hair follicles. N. Engl. J. Med. 341, 491–497 (1999).

    CAS  PubMed  Google Scholar 

Download references


I am grateful to my many colleagues who helped to establish the groundwork for this review. I also thank J.-F. Nicolas (Pasteur Institute), H. A. Pasolli, H. Rhee and T. Lechler for their helpful suggestions about figures for this review. I am especially indebted to my former mentor, H. Green, his former postdoctoral researchers — T.-T. Sun, J. Rheinwald, F. Watt and Y. Barrandon — and to the members of my laboratory, past and present, all of whom have contributed so heavily to the field of skin biology and who have served as an enormous source of inspiration to my own contributions. E.F. is an Investigator of the Howard Hughes Medical Institute. This work was supported in part by the National Institutes of Health and the Stem Cell Research Foundation.

Author information



Ethics declarations

Competing interests

The author declares no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Fuchs, E. Scratching the surface of skin development. Nature 445, 834–842 (2007).

Download citation

Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing