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Neural tube, skeletal and body wall defects in mice lacking transcription factor AP-2

Nature volume 381, pages 238–241 (1996)Cite this article

Abstract

THE retinoic acid-inducible transcription factor AP-2 is expressed in epithelial and neural crest cell lineages during murine development1–5. AP-2 can regulate neural and epithelial gene transcription, and is associated with overexpression of c-erbB-2 in human breast-cancer cell lines4–6. To ascertain the importance of AP-2 for normal development, we have derived mice containing a homozygous disruption of the AP-2 gene. These AP-2-null mice have multiple congenital defects and die at birth. In particular, the AP-2 knockout mice exhibit anencephaly, craniofacial defects and thoraco-abdominoschisis. Skeletal defects occur in the head and trunk region, where many bones are deformed or absent. Analysis of these mice earlier in embryogenesis indicates a failure of cranial neural-tube closure and defects in cranial ganglia development. We have shown that AP-2 is a fundamental regulator of mammalian craniofacial development.

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References

  1. Mitchell, P. J., Timmons, P. M., Hébert, J. M., Rigby, P. W. J. & Tijan, R. Genes Dev. 5, 105–119 (1991).

    Article  CAS  PubMed  Google Scholar 

  2. Meier, P., Koedood, M., Philipp, J., Fontana, A. & Mitchell, P. J. Devl Biol. 169, 1–14 (1995).

    Article  CAS  Google Scholar 

  3. Lüscher, B., Mitchell, P. J., Williams, T. & Tjian, R. Genes Dev. 3(10), 1507–1517 (1989).

    Article  PubMed  Google Scholar 

  4. Byrne, C., Tainsky, M. & Fuchs, E. Development 120, 2369–2383 (1994).

    CAS  PubMed  Google Scholar 

  5. Williams, T., Admon, A., Lüscher, B. & Tjian, R. Genes Dev. 2, 1557–1569 (1988).

    Article  CAS  PubMed  Google Scholar 

  6. Bosher, J. M., Williams, T. & Hurst, H. C. Proc. natn. Acad. Sci. U.S.A. 92, 744–747 (1995).

    Article  ADS  CAS  Google Scholar 

  7. Chen, J. M. J. Anat. 86, 373–386 (1952).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Hall, B. K. J. Embryol. exp. Morph. 93, 133–152 (1986).

    CAS  PubMed  Google Scholar 

  9. Davis, A. P., Witte, D. P., Hsieh-Li, H. M., Potter, S. S. & Capecchi, M. R. Nature 375, 791–795 (1995).

    Article  ADS  CAS  PubMed  Google Scholar 

  10. Le Douarin, N. M., Ziller, C. & Couly, G. F. Devl Biol. 159, 24–49 (1993).

    Article  CAS  Google Scholar 

  11. Hall, B. K. & Hörstadius, S. The Neural Crest (Oxford Univ. Press, 1988).

    Google Scholar 

  12. Copp, A. J., Brook, F. A., Estibeiro, P., Shum, A. S. W. & Cockcroft, D. L. Prog. Neurol. 35, 363–403 (1990).

    Article  CAS  Google Scholar 

  13. Echelard, Y., Vassileva, G. & McMahon, A. P. Development 120, 2213–2224 (1994).

    CAS  PubMed  Google Scholar 

  14. Morriss-Kay, G. & Chen, W.-H. Neural Tube Defects (ed. Bock, G. & Marsh, J.) 51–56 (John Wiley, Chichester, UK, 1994).

    Google Scholar 

  15. Bronner-Fraser, M. FASEB J. 8, 699–706 (1994).

    Article  CAS  PubMed  Google Scholar 

  16. Copp, A. J. Neural Tube Defects (ed. Bock, G. & Marsh, J.) 118–134 (John Wiley, Chichester, UK, 1994).

    Google Scholar 

  17. Chen, Z.-F. & Behringer, R. R. Genes Dev. 9, 686–699 (1995).

    Article  CAS  PubMed  Google Scholar 

  18. Günther, T., Struwe, M., Aguzzi, A. & Schughart, K. Development 120, 3119–3130 (1994).

    PubMed  Google Scholar 

  19. Stumpo, D. J., Bock, C. B., Tuttle, J. S. & Blackshear, P. J. Proc. natn. Acad. Sci. U.S.A. 92, 944–948 (1995).

    Article  ADS  CAS  Google Scholar 

  20. Morriss-Kay, G. Bioessays 15, 9–15 (1993).

    Article  CAS  PubMed  Google Scholar 

  21. Kotch, L. E. & Sulik, K. K. Am. J. med. Genet. 44, 168–176 (1992).

    Article  CAS  PubMed  Google Scholar 

  22. Wei, X. & Sulik, K. K. Am. J. med. Genet 47, 862–871 (1993).

    Article  CAS  PubMed  Google Scholar 

  23. Davies, A. F. et al. Hum. molec. Genet. 4, 121–128 (1995).

    Article  CAS  PubMed  Google Scholar 

  24. Warren, G., Gordon, M., Siracusa, L. D., Buchberg, A. M. & Williams, T. Genomics 31, 234–237 (1996).

    Article  CAS  PubMed  Google Scholar 

  25. Williams, T. & Tjian, R. Genes Dev. 5, 670–682 (1991).

    Article  CAS  PubMed  Google Scholar 

  26. Williams, T. & Tjian, R. Science 251, 1067–1071 (1991).

    Article  ADS  CAS  PubMed  Google Scholar 

  27. Kuida, K. et al. Science 267, 2000–2003 (1995).

    Article  ADS  CAS  PubMed  Google Scholar 

  28. Martin, J. F., Bradley, A. & Olson, E. N. Genes Dev. 9, 1237–1249 (1995).

    Article  CAS  PubMed  Google Scholar 

  29. Matsuo, I., Kuratani, S., Kimura, C., Takeda, N. & Aizawa, S. Genes Dev. 9, 2646–2658 (1995).

    Article  CAS  PubMed  Google Scholar 

  30. Mark, M. et al. Development 119, 319–338 (1993).

    CAS  PubMed  Google Scholar 

Download references

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Authors and Affiliations

  1. Department of Biology, Yale University, 266 Whitney Avenue, New Haven, Connecticut, 06511, USA

    Jian Zhang, Stephanie Hagopian-Donaldson, Debora Plehn-Dujowich & Trevor Williams

  2. Department of Cellular and Developmental Biology, The Biological Laboratories, Harvard University, 16 Divinity Avenue, Cambridge, Massachusetts, 02138, USA

    George Serbedzija & Andrew P. McMahon

  3. Howard Hughes Medical Institute and Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, 06510, USA

    Jennifer Elsemore & Richard A. Flavell

Authors
  1. Jian Zhang
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  2. Stephanie Hagopian-Donaldson
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  8. Trevor Williams
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Zhang, J., Hagopian-Donaldson, S., Serbedzija, G. et al. Neural tube, skeletal and body wall defects in mice lacking transcription factor AP-2. Nature 381, 238–241 (1996). https://doi.org/10.1038/381238a0

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