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Epidermal JunB represses G-CSF transcription and affects haematopoiesis and bone formation

Nature Cell Biology volume 10, pages 1003–1011 (2008)Cite this article

Abstract

Mice that lack JunB in epidermal cells are born with normal skin; however, keratinocytes hyperproliferate in vitro and on TPA treatment in vivo. Loss of JunB expression in the epidermis of adult mice affects the skin, the proliferation of haematopoietic cells and bone formation. G-CSF is a direct transcriptional target of JunB and mutant epidermis releases large amounts of G-CSF that reach high systemic levels and cause skin ulcerations, myeloproliferative disease and low bone mass. The absence of G-CSF significantly improves hyperkeratosis and prevents the development of myeloproliferative disease, but does not affect bone loss. This study describes a mechanism by which the absence of JunB in epithelial cells causes multi-organ disease, suggesting that the epidermis can act as an endocrine-like organ.

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Figure 1: Epithelial-specific deletion of JunB induces keratinocyte proliferation and enhances the stress response to TPA.
Figure 2: Myeloproliferative disease (MPD) and osteopaenia in JunBΔep mice.
Figure 3: Increased G-CSF expression in JunBΔep mice.
Figure 4: JunB directly regulates G-CSF transcription in keratinocytes.
Figure 5: JunBΔep mice lacking G-CSF do not develop myeloproliferative disease (MPD).

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Acknowledgements

We are very grateful to P. Angel, R. Eferl, D. Maurer, E. Passegué, A. J. Pospisilik, M. Sibilia and J. Guinea Viniegra for critical comments and suggestions to the manuscript; A. Bozec and V. Komnenovic for invaluable support for bone histology, U. Möhle-Steinlein for Southern blots and H. Tkadletz for help in preparing the illustrations. The IMP is funded by Boehringer Ingelheim and this work was supported by grants P14680-Gen and P18478 from the Austrian Research Foundation, by the Research Training Network (RTN) Program of the European Community and part of this work was supported by an FWF Network grant NFN S94-SP11. IMBA is founded by the Ministry of Science and the Austrian Academy of Sciences. JMP is also supported by grants from the Austrian Research Foundation (SFB).

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Author notes

  1. Arabella Meixner, Helia B Schonthaler & Erwin F. Wagner

    Present address: Cancer Cell Biology Programme, Centro Nacional de Investigaciones Oncológicas (CNIO), Melchor Fernández Almagro, 3, Madrid, E-28029, Spain

  2. Arabella Meixner and Rainer Zenz: These authors contributed equally to this work.

Authors and Affiliations

  1. Research Institute of Molecular Pathology (IMP), Dr. Bohr-Gasse 7, Vienna, A-1030, Austria

    Arabella Meixner, Rainer Zenz, Helia B Schonthaler, Lukas Kenner, Harald Scheuch & Erwin F. Wagner

  2. Institute of Molecular Biotechnology (IMBA), Dr. Bohr-Gasse 3, Vienna, A-1030, Austria

    Josef M. Penninger

  3. Ludwig Boltzmann Institute for Cancer Research (LBI-CR), Währingerstraße 13a, Vienna, A-1090, Austria

    Rainer Zenz & Lukas Kenner

  4. Institute of Clinical Pathology, Medical University of Vienna, Währingergürtel 18-20, Vienna, A-1090, Austria

    Lukas Kenner

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Contributions

A.M., R.Z., H.B.S. and E.F.W. planned and designed the experiments; A.M., R.Z., H.B.S., L.K. and H.S. performed the experiments; A.M., R.Z., H.B.S., L.K., J.M.P. and E.F.W. analysed and interpreted the data; J.M.P. contributed reagents; A.M., R.Z., H.B.S. and E.F.W. wrote the manuscript.

Corresponding author

Correspondence to Erwin F. Wagner.

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The authors declare no competing financial interests.

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Meixner, A., Zenz, R., Schonthaler, H. et al. Epidermal JunB represses G-CSF transcription and affects haematopoiesis and bone formation. Nat Cell Biol 10, 1003–1011 (2008). https://doi.org/10.1038/ncb1761

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