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.

  • Progress
  • Published:

Follow the mRNA: a new model for Bicoid gradient formation

Nature Reviews Molecular Cell Biology volume 10, pages 509–512 (2009)Cite this article

Abstract

Morphogens are molecules that specify cell fate in a concentration-dependent manner. A classic example is the Bicoid (BCD) protein, for which the prevailing model is that translation of bcd mRNA occurs from a point source at the anterior pole of the Drosophila melanogaster embryo followed by diffusion to produce a protein gradient. This model has been challenged by experiments showing that the diffusion rate of BCD is too slow to establish the protein gradient. The work described in a recent paper has solved this conundrum by demonstrating that a bcd mRNA gradient prefigures the BCD protein gradient.

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: The diffusion-based model for formation of the Bicoid protein gradient.
Figure 2: Gradients of bicoid mRNA and Bicoid protein are nearly identical in early Drosophila melanogaster embryos.
Figure 3: The active mRNA transport and local translation model for formation of the Bicoid protein gradient.

Similar content being viewed by others

References

  1. Turing, A. M. The chemical basis of morphogenesis. Philos. Trans. Roy. Soc. (Lond) 237, 37–72 (1952).

    Google Scholar 

  2. Gierer, A. & Meinhardt, H. A theory of biological pattern formation. Kybernetik 12, 30–39 (1972).

    Article  CAS  PubMed  Google Scholar 

  3. Wolpert, L. Positional information and pattern formation. Curr. Top. Dev. Biol. 6, 183–224 (1971).

    Article  CAS  PubMed  Google Scholar 

  4. Zecca, M., Basler, K. & Struhl, G. Direct and long-range action of a wingless morphogen gradient. Cell 87, 833–844 (1996).

    Article  CAS  PubMed  Google Scholar 

  5. Nellen, D., Burke, R., Struhl, G. & Basler, K. Direct and long-range action of a DPP morphogen gradient. Cell 85, 357–368 (1996).

    Article  CAS  PubMed  Google Scholar 

  6. Lawrence, P. A., Casal, J. & Struhl, G. The hedgehog morphogen and gradients of cell affinity in the abdomen of Drosophila. Development 126, 2441–2449 (1999).

    CAS  PubMed  Google Scholar 

  7. Heemskerk, J. & DiNardo, S. Drosophila hedgehog acts as a morphogen in cellular patterning. Cell 76, 449–460 (1994).

    Article  CAS  PubMed  Google Scholar 

  8. Frohnhöfer, H. G. & Nüsslein-Volhard, C. Organization of anterior pattern in the Drosophila embryo by the maternal gene bicoid. Nature 324, 120–125 (1986).

    Article  Google Scholar 

  9. Driever, W. & Nüsslein-Volhard, C. A gradient of bicoid protein in Drosophila embryos. Cell 54, 83–93 (1988).

    Article  CAS  PubMed  Google Scholar 

  10. Struhl, G., Struhl, K. & Macdonald, P. M. The gradient morphogen bicoid is a concentration-dependent transcriptional activator. Cell 57, 1259–1273 (1989).

    Article  CAS  PubMed  Google Scholar 

  11. Driever, W., Siegel, V. & Nüsslein-Volhard, C. Autonomous determination of anterior structures in the early Drosophila embryo by the bicoid morphogen. Development 109, 811–820 (1990).

    CAS  PubMed  Google Scholar 

  12. Frigerio, G., Burri, M., Bopp, D., Baumgartner, S. & Noll, M. Structure of the segmentation gene paired and the Drosophila PRD gene set as part of a gene network. Cell 47, 735–746 (1986).

    Article  CAS  PubMed  Google Scholar 

  13. Kornberg, T. B. & Guha, A. Understanding morphogen gradients: a problem of dispersion and containment. Curr. Opin. Genet. Dev. 17, 264–271 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Gregor, T., Tank, D. W., Wieschaus, E. F. & Bialek, W. Probing the limits to positional information. Cell 130, 153–164 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Gregor, T., Wieschaus, E. F., McGregor, A. P., Bialek, W. & Tank, D. W. Stability and nuclear dynamics of the bicoid morphogen gradient. Cell 130, 141–152 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Spirov, A. et al. Formation of the bicoid morphogen gradient: an mRNA gradient dictates the protein gradient. Development 136, 605–614 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Driever, W. & Nüsslein-Volhard, C. The bicoid protein determines position in the Drosophila embryo in a concentration-dependent manner. Cell 54, 95–104 (1988).

    Article  CAS  PubMed  Google Scholar 

  18. Driever, W. & Nüsslein-Volhard, C. The bicoid protein is a positive regulator of hunchback transcription in the early Drosophila embryo. Nature 337, 138–143 (1989).

    Article  CAS  PubMed  Google Scholar 

  19. Burz, D. S., Rivera-Pomar, R., Jackle, H. & Hanes, S. D. Cooperative DNA-binding by Bicoid provides a mechanism for threshold-dependent gene activation in the Drosophila embryo. EMBO J. 17, 5998–6009 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Driever, W., Thoma, G. & Nusslein-Volhard, C. Determination of spatial domains of zygotic gene expression in the Drosophila embryo by the affinity of binding sites for the bicoid morphogen. Nature 340, 363–367 (1989).

    Article  CAS  PubMed  Google Scholar 

  21. Rivera-Pomar, R., Niessing, D., Schmidt-Ott, U., Gehring, W. J. & Jackle, H. RNA binding and translational suppression by bicoid. Nature 379, 746–749 (1996).

    Article  CAS  PubMed  Google Scholar 

  22. Dubnau, J. & Struhl, G. RNA recognition and translational regulation by a homeodomain protein. Nature 379, 694–699 (1996).

    Article  CAS  PubMed  Google Scholar 

  23. Weil, T. T., Parton, R., Davis, I. & Gavis, E. R. Changes in bicoid mRNA anchoring highlight conserved mechanisms during the oocyte-to-embryo transition. Curr. Biol. 18, 1055–1061 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Ferrandon, D., Elphick, L., Nüsslein-Volhard, C. & St Johnston, D. Staufen protein associates with the 3'UTR of bicoid mRNA to form particles that move in a microtubule-dependent manner. Cell 79, 1221–1232 (1994).

    Article  CAS  PubMed  Google Scholar 

  25. Zimyanin, V. L. et al. In vivo imaging of oskar mRNA transport reveals the mechanism of posterior localization. Cell 134, 843–853 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Mlodzik, M. & Gehring, W. J. Expression of the caudal gene in the germ line of Drosophila: formation of an RNA and protein gradient during early embryogenesis. Cell 48, 465–478 (1987).

    Article  CAS  PubMed  Google Scholar 

  27. Macdonald, P. M. & Struhl, G. A molecular gradient in early Drosophila embryos and its role in specifying the body pattern. Nature 324, 537–545 (1986).

    Article  CAS  PubMed  Google Scholar 

  28. Cho, P. F. et al. A new paradigm for translational control: inhibition via 5′-3′ mRNA tethering by Bicoid and the eIF4E cognate 4EHP. Cell 121, 411–423 (2005).

    Article  CAS  PubMed  Google Scholar 

  29. Schulz, C., Schroder, R., Hausdorf, B., Wolff, C. & Tautz, D. A caudal homologue in the short germ band beetle Tribolium shows similarities to both the Drosophila and the vertebrate caudal expression patterns. Dev. Genes Evol. 208, 283–289 (1998).

    Article  CAS  PubMed  Google Scholar 

  30. Olesnicky, E. C. et al. A caudal mRNA gradient controls posterior development in the wasp Nasonia. Development 133, 3973–3982 (2006).

    Article  CAS  PubMed  Google Scholar 

  31. Bucher, G., Farzana, L., Brown, S. J. & Klingler, M. Anterior localization of maternal mRNAs in a short germ insect lacking bicoid. Evol. Dev. 7, 142–149 (2005).

    Article  CAS  PubMed  Google Scholar 

  32. Lynch, J. A., Brent, A. E., Leaf, D. S., Pultz, M. A. & Desplan, C. Localized maternal orthodenticle patterns anterior and posterior in the long germ wasp Nasonia. Nature 439, 728–732 (2006).

    Article  CAS  PubMed  Google Scholar 

  33. Dubrulle, J. & Pourquie, O. fgf8 mRNA decay establishes a gradient that couples axial elongation to patterning in the vertebrate embryo. Nature 427, 419–422 (2004).

    Article  CAS  PubMed  Google Scholar 

  34. Lecuyer, E. et al. Global analysis of mRNA localization reveals a prominent role in organizing cellular architecture and function. Cell 131, 174–187 (2007).

    Article  CAS  PubMed  Google Scholar 

  35. De Renzis, S., Elemento, O., Tavazoie, S. & Wieschaus, E. F. Unmasking activation of the zygotic genome using chromosomal deletions in the Drosophila embryo. PLoS Biol. 5, e117 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  36. Tadros, W. et al. SMAUG is a major regulator of maternal mRNA destabilization in Drosophila and its translation is activated by the PAN GU kinase. Dev. Cell 12, 143–155 (2007).

    Article  CAS  PubMed  Google Scholar 

  37. Bashirullah, A. et al. Joint action of two RNA degradation pathways controls the timing of maternal transcript elimination at the midblastula transition in Drosophila melanogaster. EMBO J. 18, 2610–2620 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Sincere thanks to M. Noll and S. Baumgartner for providing the images used in figure 2. H.D.L.'s research on post-transcriptional regulation in D. melanogaster is supported by the Canadian Institutes for Health Research in the form of an operating grant (MOP-14409) and a team grant (CIHR Team in mRNP Systems Biology; CTP-79838).

Author information

Authors and Affiliations

  1. Department of Molecular Genetics and the Hospital for Sick Children Research Institute Program in Developmental and Stem Cell Biology, Howard D. Lipshitz is at the University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8 Canada. howard.lipshitz@utoronto.ca,

    Howard D. Lipshitz

Authors
  1. Howard D. Lipshitz
    View author publications

    You can also search for this author in PubMed Google Scholar

Related links

Related links

FURTHER INFORMATION

Howard D. Lipshitz's homepage

Flybase

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lipshitz, H. Follow the mRNA: a new model for Bicoid gradient formation. Nat Rev Mol Cell Biol 10, 509–512 (2009). https://doi.org/10.1038/nrm2730

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrm2730

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing