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A conserved retinoic acid response element required for early expression of the homeobox gene Hoxb-1

Abstract

WITHIN the Hoxb homeobox gene complex, Hoxb-1 is the earliest member expressed in the mesoderm and neuroectoderm of primitive streak and presomite embryos, preceding rhombomere-restricted expression in the hind brain1–7. Ectopic exposure of embryos to retinoic acid alters spatial aspects of Hox gene expression patterns8–15. However, the role of retinoids in regulating these genes during normal development is unclear. We have now identified two enhancers, 3′ of the mouse Hoxb-1 gene, which together reconstruct the early endogenous expression pattern and mediate the early ectopic response to retinoic acid. Furthermore, these regions are functionally conserved in both chicken and pufferfish (Fugu rubripes)16 Hoxb-1 genes. The enhancer that controls the retinoic acid response, and regulates expression predominantly in neuroectoderm, contains a retinoic acid response element (RARE). Point mutations in the RARE abolish expression in neuroectoderm. Therefore, this RARE is not only involved in the ectopic response to retinoic acid, but is also essential for establishing aspects of the early Hoxb-l expression pattern.

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References

  1. Wilkinson, D. et al. Nature 341, 405–409 (1989).

    Article  ADS  CAS  Google Scholar 

  2. Murphy, P., Davidson, D. & Hill, R. Nature 341, 156–159 (1989).

    Article  ADS  CAS  Google Scholar 

  3. Frohman, M., Boyle, M. & Martin, G. Development 110, 589–607 (1990).

    CAS  PubMed  Google Scholar 

  4. Sundin, O. & Eichele, G. Genes Dev. 4, 1267–1276 (1990).

    Article  CAS  Google Scholar 

  5. Maden, M. et al. Development 111, 35–44 (1991).

    CAS  PubMed  Google Scholar 

  6. Guthrie, S. et al. Nature 356, 157–159 (1992).

    Article  ADS  CAS  Google Scholar 

  7. Murphy, P. & Hill, R. Development 111, 61–74 (1991).

    CAS  Google Scholar 

  8. Conlon, R. & Rossant, J. Development 116, 357–368 (1992).

    CAS  PubMed  Google Scholar 

  9. Marshall, H. et al. Nature 360, 737–741 (1992).

    Article  ADS  CAS  Google Scholar 

  10. Sundin, O. & Eichele, G. Development 114, 841–852 (1992).

    CAS  Google Scholar 

  11. Kessel, M. Neuron 10, 379–393 (1993).

    Article  CAS  Google Scholar 

  12. Morriss-Kay, G. et al. EMBO J. 10, 2985–2996 (1991).

    Article  CAS  Google Scholar 

  13. Kessel, M. & Gruss, P. Cell 67, 89–104 (1991).

    Article  CAS  Google Scholar 

  14. Dolle, P. et al. Nature 342, 767–772 (1989).

    Article  ADS  CAS  Google Scholar 

  15. Izpisua-Belmonte, J.-C. et al. Nature 350, 585–589 (1991).

    Article  ADS  CAS  Google Scholar 

  16. Brenner, S. et al. Nature 366, 265–268 (1993).

    Article  ADS  CAS  Google Scholar 

  17. Leid, M., Kastner, P. & Chambon, P. Trends biochem. Sci. 17, 427–433 (1992).

    Article  CAS  Google Scholar 

  18. Stunnenberg, H. Bioessays 15, 309–315 (1993).

    Article  CAS  Google Scholar 

  19. Kliewer, S. A. et al. Nature 355, 446–449 (1992).

    Article  ADS  CAS  Google Scholar 

  20. Durston, A. et al. Nature 340, 140–144 (1989).

    Article  ADS  CAS  Google Scholar 

  21. Ruiz i Altaba, A. & Jessell, T. Genes Dev. 5, 175–187 (1991).

    Article  CAS  Google Scholar 

  22. Ruiz i Altaba, A. & Jessell, T. Development 112, 945–958 (1991).

    CAS  PubMed  Google Scholar 

  23. Papalopulu, N. et al. Development 113, 1145–1159 (1991).

    CAS  PubMed  Google Scholar 

  24. Sive, H. & Cheng, P. Genes Dev. 5, 1321–1332 (1991).

    Article  CAS  Google Scholar 

  25. Sive, H. et al. Genes Dev. 4, 932–942 (1990).

    Article  CAS  Google Scholar 

  26. Holder, N. & Hill, J. Development 113, 1159–1170 (1991).

    CAS  PubMed  Google Scholar 

  27. Langston, A. W. & Gudas, L. J. Mechanisms of Development 38, 217–228 (1992).

    Article  CAS  Google Scholar 

  28. Whiting, J. et al. Genes Dev. 5, 2048–2059 (1991).

    Article  CAS  Google Scholar 

  29. Yee, S.-P. & Rigby, P. W. R. Genes Dev. 7, 1277–1289 (1993).

    Article  CAS  Google Scholar 

  30. Popperl, H. & Featherstone, M. S. Molec. cell. Biol. 13, 257–265 (1993).

    Article  CAS  Google Scholar 

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Marshall, H., Studer, M., Pöpperl, H. et al. A conserved retinoic acid response element required for early expression of the homeobox gene Hoxb-1. Nature 370, 567–571 (1994). https://doi.org/10.1038/370567a0

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