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Collinear activation of Hoxb genes during gastrulation is linked to mesoderm cell ingression

Nature volume 442, pages 568–571 (2006)Cite this article

Abstract

The vertebral column exhibits segmentation and regionalization along the antero-posterior axis. During embryogenesis, the rhythmic production of the precursors of the vertebrae, the somites, imposes a segmented aspect to the spine, whereas the spine's regional differentiation is controlled by Hox genes1,2. Here we show that in the paraxial mesoderm, Hoxb genes are first activated in a temporal collinear fashion in precursors located in the epiblast lateral to the primitive streak. Our data suggest that collinear activation of Hoxb genes regulates the flux of cells from the epiblast to the streak and thus directly controls the establishment of the genes' characteristic nested expression domains in the somites. This suggests that establishment of the spatial co-linearity in the embryo is directly controlled by the Hox genes themselves.

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Figure 1: Hox gene activation begins in the mesodermal territory of the epiblast.
Figure 2: Hox genes control the timing of ingression of epiblast cells into the primitive streak.
Figure 3: Posterior prevalence of Hoxb genes.
Figure 4: Heterochronic grafts of the primitive streak.

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References

  1. Kmita, M. & Duboule, D. Organizing axes in time and space; 25 years of colinear tinkering. Science 301, 331–333 (2003)

    Article  ADS  CAS  Google Scholar 

  2. Krumlauf, R. Hox genes in vertebrate development. Cell 78, 191–201 (1994)

    Article  CAS  Google Scholar 

  3. Dolle, P., Izpisua-Belmonte, J. C., Falkenstein, H., Renucci, A. & Duboule, D. Coordinate expression of the murine Hox-5 complex homoeobox-containing genes during limb pattern formation. Nature 342, 767–772 (1989)

    Article  ADS  CAS  Google Scholar 

  4. Gaunt, S. J., Sharpe, P. T. & Duboule, D. Spatially restricted domains of homeo-gene transcripts in mouse embryos: relation to a segmented body plan. Development 104, 169–179 (1988)

    Google Scholar 

  5. Graham, A., Papalopulu, N. & Krumlauf, R. The murine and Drosophila homeobox gene complexes have common features of organization and expression. Cell 57, 367–378 (1989)

    Article  CAS  Google Scholar 

  6. Kessel, M. & Gruss, P. Homeotic transformations of murine vertebrae and concomitant alteration of Hox codes induced by retinoic acid. Cell 67, 89–104 (1991)

    Article  CAS  Google Scholar 

  7. Wellik, D. M. & Capecchi, M. R. Hox10 and Hox11 genes are required to globally pattern the mammalian skeleton. Science 301, 363–367 (2003)

    Article  ADS  CAS  Google Scholar 

  8. Deschamps, J. & van Nes, J. Developmental regulation of the Hox genes during axial morphogenesis in the mouse. Development 132, 2931–2942 (2005)

    Article  CAS  Google Scholar 

  9. Wacker, S. A., Jansen, H. J., McNulty, C. L., Houtzager, E. & Durston, A. J. Timed interactions between the Hox expressing non-organiser mesoderm and the Spemann organiser generate positional information during vertebrate gastrulation. Dev. Biol. 268, 207–219 (2004)

    Article  CAS  Google Scholar 

  10. Forlani, S., Lawson, K. A. & Deschamps, J. Acquisition of Hox codes during gastrulation and axial elongation in the mouse embryo. Development 130, 3807–3819 (2003)

    Article  CAS  Google Scholar 

  11. Stern, C. D. in Gastrulation: From Cells to Embryos (ed. Stern, C. D.) 219–232 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, 2004)

    Google Scholar 

  12. Garcia-Martinez, V., Alvarez, I. S. & Schoenwolf, G. C. Locations of the ectodermal and nonectodermal subdivisions of the epiblast at stages 3 and 4 of avian gastrulation and neurulation. J. Exp. Zool. 267, 431–446 (1993)

    Article  CAS  Google Scholar 

  13. Nicolet, G. Avian gastrulation. Adv. Morphog. 9, 231–262 (1971)

    Article  CAS  Google Scholar 

  14. Greer, J. M., Puetz, J., Thomas, K. R. & Capecchi, M. R. Maintenance of functional equivalence during paralogous Hox gene evolution. Nature 403, 661–665 (2000)

    Article  ADS  CAS  Google Scholar 

  15. Stewart, C. L., Schuetze, S., Vanek, M. & Wagner, E. F. Expression of retroviral vectors in transgenic mice obtained by embryo infection. EMBO J. 6, 383–388 (1987)

    Article  CAS  Google Scholar 

  16. Stamataki, D., Ulloa, F., Tsoni, S. V., Mynett, A. & Briscoe, J. A gradient of Gli activity mediates graded Sonic Hedgehog signaling in the neural tube. Genes Dev. 19, 626–641 (2005)

    Article  CAS  Google Scholar 

  17. Duboule, D. & Morata, G. Colinearity and functional hierarchy among genes of the homeotic complexes. Trends Genet. 10, 358–364 (1994)

    Article  CAS  Google Scholar 

  18. Tam, P. P. & Tan, S. S. The somitogenetic potential of cells in the primitive streak and the tail bud of the organogenesis-stage mouse embryo. Development 115, 703–715 (1992)

    CAS  PubMed  Google Scholar 

  19. Hamburger, V. & Hamilton, H. L. A series of normal stages in the development of the chick embryo. Dev. Dyn. 195, 231–272 (1992)

    Article  CAS  Google Scholar 

  20. Henrique, D. et al. Expression of a Delta homologue in prospective neurons in the chick. Nature 375, 787–790 (1995)

    Article  ADS  CAS  Google Scholar 

  21. Bel-Vialar, S., Itasaki, N. & Krumlauf, R. Initiating Hox gene expression: in the early chick neural tube differential sensitivity to FGF and RA signaling subdivides the HoxB genes in two distinct groups. Development 129, 5103–5115 (2002)

    CAS  PubMed  Google Scholar 

  22. Chapman, S. C., Collignon, J., Schoenwolf, G. C. & Lumsden, A. Improved method for chick whole-embryo culture using a filter paper carrier. Dev. Dyn. 220, 284–289 (2001)

    Article  CAS  Google Scholar 

  23. Yang, X., Dormann, D., Munsterberg, A. E. & Weijer, C. J. Cell movement patterns during gastrulation in the chick are controlled by positive and negative chemotaxis mediated by FGF4 and FGF8. Dev. Cell 3, 425–437 (2002)

    Article  CAS  Google Scholar 

  24. Niwa, H., Yamamura, K. & Miyazaki, J. Efficient selection for high-expression transfectants with a novel eukaryotic vector. Gene 108, 193–199 (1991)

    Article  CAS  Google Scholar 

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Acknowledgements

We thank S. Abmayr, R. Krumlauf and D. Wellik for comments on the manuscript; X.-S. Yang and C. Weijer for sharing their expertise in fate mapping and for discussions; members of the Pourquié laboratory for sharing reagents and for discussions; C. Tomomori-Sato and S. Sato of the Conaway laboratory for discussions; and S. Esteban for artwork. This work was supported by the Stowers Institute for Medical Research and the NIH. O.P. is a Howard Hughes Medical Institute Investigator.

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  1. Howard Hughes Medical Institute and Stowers Institute for Medical Research, 1000 E. 50th Street, Missouri, 64110, Kansas City, USA

    Tadahiro Iimura & Olivier Pourquié

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  1. Tadahiro Iimura
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  2. Olivier Pourquié
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Correspondence to Olivier Pourquié.

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Supplementary information

Supplementary Figure 1

Double whole mount in situ hybridization of Sox 2 and HoxB7. Onset of Hoxb7 expression (blue) is in the epiblast adjacent to the primitive streak and this Hox domain is at a distance from the neural territory marked by Sox2 (red). (PDF 189 kb)

Supplementary Tables

Supplementary Tables 1–3 show the result of each experiment in which caudal-most and rostral-most distribution of labeled cells by Hox-reporter construct were scored by somite number along anterior-posterior axis. The stage and area of each embryo at which graft and/or electroporation were carried out are also indicated. Supplementary Table 1 is a summary of Hox electroporation and graft experiments. Supplementary Table 2 is a summary of successive Hox electroporation experiments. Supplementary Table 3 is a summary of Heterochronic graft experiments. (PDF 31 kb)

Supplementary Methods

This file contains additional details of the methods used in this study. (DOC 27 kb)

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Iimura, T., Pourquié, O. Collinear activation of Hoxb genes during gastrulation is linked to mesoderm cell ingression. Nature 442, 568–571 (2006). https://doi.org/10.1038/nature04838

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