Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Hair cycle and wound healing in mice with a keratinocyte-restricted deletion of FAK

Oncogene volume 25, pages 1081–1089 (2006)Cite this article

Abstract

Focal adhesion kinase (FAK) is a critical component in transducing signals downstream of both integrins and growth factor receptors. To determine how the loss of FAK affects the epidermis in vivo, we have generated a mouse model with a keratinocyte-restricted deletion of fak (FAKK5 KO mice). FAKK5 KO mice displayed three major phenotypes – irregularities of hair cycle, sebaceous glands hypoplasia, and a thinner epidermis – pointing to defects in the proliferative capacity of multipotent stem cells found in the bulge. FAK-null keratinocytes in conventional primary culture undergo massive apoptosis hindering further analyses, whereas the defects observed in vivo do not shorten the mouse lifespan. These results suggest that the structure and the signaling environment of the native tissue may overcome the lack of signaling through FAK. Our findings point to the importance of in vivo and three-dimensional in vitro models in analyses of cell migration, proliferation, and survival. Surprisingly, the difference between FAKloxP/+ and FAKK5 KO mice in wound closure was not statistically significant, suggesting that in vivo loss of FAK does not affect migration/proliferation of basal keratinocytes in the same way as it affects multipotent stem cells of the skin.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

Abbreviations

E:

embryonic day

ECM:

extracellular matrix

P:

postnatal day

References

  • Abbi S, Guan JL . (2002). Histol Histopathol 17: 1163–1171.

  • Adams JC, Watt FM . (1989). Nature 340: 307–309.

  • Alonso L, Fuchs E . (2003). Proc Natl Acad Sci USA 100: 11830–11835.

  • Andre E, Becker-Andre M . (1993). Biochem Biophys Res Commun 190: 140–147.

  • Beggs HE, Schahin-Reed D, Zang K, Goebbels S, Nave KA, Gorski J et al. (2003). Neuron 40: 501–514.

  • Brakebusch C, Grose R, Quondamatteo F, Ramirez A, Jorcano JL, Pirro A et al. (2000). EMBO J 19: 3990–4003.

  • Cary LA, Chang JF, Guan JL . (1996). J Cell Sci 109: 1787–1794.

  • Coulombe PA . (1997). Biochem Biophys Res Commun 236: 231–238.

  • Cui CY, Durmowicz M, Ottolenghi C, Hashimoto T, Griggs B, Srivastava AK et al. (2003). Hum Mol Genet 12: 2931–2940.

  • Damsky CH, Ilic D . (2002). Curr Opin Cell Biol 14: 594–602.

  • Fincham VJ, Frame MC . (1998). EMBO J 17: 81–92.

  • Frisch SM, Vuori K, Ruoslahti E, Chan-Hui PY . (1996). J Cell Biol 134: 793–799.

  • Furuta Y, Ilic D, Kanazawa S, Takeda N, Yamamoto T, Aizawa S . (1995). Oncogene 11: 1989–1995.

  • Grose R, Hutter C, Bloch W, Thorey I, Watt FM, Fassler R et al. (2002). Development 129: 2303–2315.

  • Hanks SK, Ryzhova L, Shin NY, Brabek J . (2003). Front Biosci 8: d982–d996.

  • Hauck CR, Sieg DJ, Hsia DA, Loftus JC, Gaarde WA, Monia BP et al. (2001). Cancer Res 61: 7079–7090.

  • Ilic D, Almeida EA, Schlaepfer DD, Dazin P, Aizawa S, Damsky CH . (1998). J Cell Biol 143: 547–560.

  • Ilic D, Furuta Y, Kanazawa S, Takeda N, Sobue K, Nakatsuji N et al. (1995a). Nature 377: 539–544.

  • Ilic D, Furuta Y, Suda T, Atsumi T, Fujimoto J, Ikawa Y et al. (1995b). Biochem Biophys Res Commun 209: 300–309.

  • Ilic D, Genbacev O, Jin F, Caceres E, Almeida EA, Bellingard-Dubouchaud V et al. (2001). Am J Pathol 159: 93–108.

  • Ilic D, Kovacic B, Johkura K, Schlaepfer DD, Tomasevic N, Han Q et al. (2004). J Cell Sci 117: 177–187.

  • Klemke RL, Leng J, Molander R, Brooks PC, Vuori K, Cheresh DA . (1998). J Cell Biol 140: 961–972.

  • Kovacic-Milivojevic B, Roediger F, Almeida EA, Damsky CH, Gardner DG, Ilic D . (2001). Mol Biol Cell 12: 2290–2307.

  • Liu Y, Lyle S, Yang Z, Cotsarelis G . (2003). J Invest Dermatol 121: 963–968.

  • Ma DR, Yang EN, Lee ST . (2004). Ann Acad Med Singapore 33: 784–788.

  • McLean GW, Avizienyte E, Frame MC . (2003). Expert Opin Pharmacother 4: 227–234.

  • McLean GW, Komiyama NH, Serrels B, Asano H, Reynolds L, Conti F et al. (2004). Genes Dev 18: 2998–3003.

  • Mitra SK, Hanson DA, Schlaepfer DD . (2005). Nat Rev Mol Cell Biol 6: 56–68.

  • Morasso MI, Tomic-Canic M . (2005). Biol Cell 97: 173–183.

  • Nolan K, Lacoste J, Parsons JT . (1999). Mol Cell Biol 19: 6120–6129.

  • Oktay M, Wary KK, Dans M, Birge RB, Giancotti FG . (1999). J Cell Biol 145: 1461–1469.

  • Parsons JT . (2003). J Cell Sci 116: 1409–1416.

  • Paus R, Muller-Rover S, Van Der Veen C, Maurer M, Eichmuller S, Ling G et al. (1999). J Invest Dermatol 113: 523–532.

  • Raghavan S, Bauer C, Mundschau G, Li Q, Fuchs E . (2000). J Cell Biol 150: 1149–1160.

  • Ramirez A, Page A, Gandarillas A, Zanet J, Pibre S, Vidal M et al. (2004). Genesis 39: 52–57.

  • Schlaepfer DD, Hanks SK, Hunter T, van der Geer P . (1994). Nature 372: 786–791.

  • Schlaepfer DD, Mitra SK, Ilic D . (2004). Biochim Biophys Acta 1692: 77–102.

  • Sieg DJ, Hauck CR, Ilic D, Klingbeil CK, Schaefer E, Damsky CH et al. (2000). Nat Cell Biol 2: 249–256.

  • Stenn KS, Paus R . (2001). Physiol Rev 81: 449–494.

  • Tumbar T, Guasch G, Greco V, Blanpain C, Lowry WE, Rendl M et al. (2004). Science 303: 359–363.

  • Vaezi A, Bauer C, Vasioukhin V, Fuchs E . (2002). Dev Cell 3: 367–381.

  • Wary KK, Mariotti A, Zurzolo C, Giancotti FG . (1998). Cell 94: 625–634.

  • Zhu AJ, Haase I, Watt FM . (1999). Proc Natl Acad Sci USA 96: 6728–6733.

Download references

Acknowledgements

The work is supported by grant from National Cancer Institute (CA87652) to D Ilic. We thank Drs C Damsky and D Schlaepfer (Scripps) for a critical reading of the manuscript and E Gering (SFSU) for editorial assistance. This investigation was conducted in a facility constructed with support from the Research Facilities Improvement Program Grant number C06RR16490.

Author information

Authors and Affiliations

  1. Department of Cell and Tissue Biology, University of California San Francisco, San Francisco, CA, USA

    S Essayem, B Kovacic-Milivojevic, C Baumbusch, S McDonagh, K Howerton, N Larocque, S J Fisher & D Ilic

  2. Department of Pulmonary, University of California San Francisco, San Francisco, CA, USA

    G Dolganov

  3. Department of Dermatology, University of California San Francisco, San Francisco, CA, USA

    T Mauro

  4. Department of Epithelial Damage, Repair and Tissue Engineering Program, CIEMAT, Madrid, Spain

    A Ramirez & J L Jorcano

  5. Department of Orofacial Sciences, University of California San Francisco, San Francisco, CA, USA

    D M Ramos

  6. Department of Physiology, University of California San Francisco, San Francisco, CA, USA

    H E Beggs & L F Reichardt

  7. Department of Ophthalmology, University of California San Francisco, San Francisco, CA, USA

    H E Beggs

Authors
  1. S Essayem
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B Kovacic-Milivojevic
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C Baumbusch
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S McDonagh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G Dolganov
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. K Howerton
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. N Larocque
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. T Mauro
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. A Ramirez
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. D M Ramos
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. S J Fisher
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. J L Jorcano
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. H E Beggs
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. L F Reichardt
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. D Ilic
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D Ilic.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Essayem, S., Kovacic-Milivojevic, B., Baumbusch, C. et al. Hair cycle and wound healing in mice with a keratinocyte-restricted deletion of FAK. Oncogene 25, 1081–1089 (2006). https://doi.org/10.1038/sj.onc.1209130

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1209130

Keywords

This article is cited by

Search

Advanced search

Quick links