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.

The Rx homeobox gene is essential for vertebrate eye development

Nature volume 387, pages 603–607 (1997)Cite this article

Abstract

Development of the vertebrate eye requires a series of steps including specification of the anterior neural plate, evagination of the optic vesicles from the ventral forebrain, and the cellular differentiation of the lens and retina. Homeobox-containing genes, especially the transcription regulator Pax6, play a critical role in vertebrate and invertebrate eye formation. Mutations in Pax6 function result in eye malformations known as Aniridia in humans and Small eye syndrome in mice1,2,3. The Drosophila homologue of Pax6, eyeless, is also necessary for correct invertebrate eye development, and its misexpression leads to formation of ectopic eyes in Drosophila4,5. Here we show that a conserved vertebrate homeobox gene, Rx, is essential for normal eye development, and that its misexpression has profound effects on eye morphology. Xenopus embryos injected with synthetic Rx RNA develop ectopic retinal tissue and display hyperproliferation in the neuroretina. Mouse embryos carrying a null allele of this gene do not form optic cups and so do not develop eyes. The Rx gene family plays an important role in the establishment and/or proliferation of retinal progenitor cells.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

Buy

All prices are NET prices.

Figure 1: Comparison of the amino-acid sequences of Xenopus and murine Rx genes.
Figure 2: Whole-mount in situ hybridization to Xenopus embryos.
Figure 3: In situ hybridizations with Mrx probe.
Figure 4: Whole-mount in situ hybridization to zebrafish (a–f) and Drosophila (g, h) embryos.
Figure 5: Embryos injected with Rx1 RNA.
Figure 6: Schematic representation of Mrx targeted deletion strategy.

References

  1. Ton, C. C. T. et al. Positional cloning and characterization of a paired box and homeobox-containing gene from the aniridia region. Cell 67, 1059–1074 (1991).

    CAS  Article  Google Scholar 

  2. Glaser, T. et al. PAX6 gene dosage effect in a family with congenital cataracts, aniridia, anophthalmia and central nervous system defects. Nature Genet. 7, 463–471 (1994).

    CAS  Article  Google Scholar 

  3. Hill, R. E. et al. Mouse Small eye results from mutations in a paired-like homeobox-containing gene. Nature 354, 522–525 (1991).

    CAS  Article  Google Scholar 

  4. Quiring, R., Walldorf, U., Kloter, U. & Gehring, W. J. Homology of the eyeless gene of Drosophila to the Small eye in mice and Aniridia in humans. Science 265, 785–789 (1994).

    CAS  Article  Google Scholar 

  5. Halder, C., Callaerts, P. & Gehring, W. J. Induction of ectopic eyes by targeted expression of the eyeless gene in Drosophila. Science 267, 1788–1792 (1995).

    CAS  Article  Google Scholar 

  6. Jamrich, M. & Sato, S. Differential gene expression in the anterior neural plate during gastrulation of Xenopus laevis. Devellopment 105, 779–786 (1989).

    CAS  Google Scholar 

  7. Sive, H. L., Harrori, K. & Weintraub, H. Progressive determination during formation of the anteroposterior axis in Xenopus laevis. Cell 58, 171–180 (1989).

    CAS  Article  Google Scholar 

  8. Mathers, P. H., Miller, A., Doniach, T., Dirksen, M.-L. & Jamrich, M. Initiation of anterior head-specific gene expession in uncommitted ectoderm of Xenopus laevis by ammonium chloride. Dev. Biol. 171, 641–654 (1995).

    CAS  Article  Google Scholar 

  9. Bopp, D., Burri, M., Baumgartner, S., Frigerio, G. & Noll, M. Conservation of a large protein domain in the segmentation gene paired and in functionally related genes in Drosophila. Cell 47, 1033–1040 (1986).

    CAS  Article  Google Scholar 

  10. Noll, M. Evolution and role of Pax genes. Curr. Opin. Genet. Dev. 3, 595–605 (1993).

    CAS  Article  Google Scholar 

  11. Hemmati-Brivanlou, A., de la Torre, J. R., Holt, C. & Harland, R. M. Cephalic expression and molecular characterization of Xenopus En-2. Development 111, 715–724 (1991).

    CAS  PubMed  Google Scholar 

  12. Holt, C. E., Bertsch, T. W., Ellis, H. M. & Harris, W. A. Cellular determination in the Xenopus retina is independent of lineage and birth data. Neuron 1, 15–26 (1988).

    CAS  Article  Google Scholar 

  13. Stiemke, M. M. & Hollyfield, J. G. Cell birthdays in Xenopus laevis retina. Differentiation 58, 189–193 (1995).

    CAS  Article  Google Scholar 

  14. Wetts, R., Serbedzija, G. N. & Fraser, S. E. Cell lineage analysis reveals multipotent precursors in the ciliary margin of the frog retina. Dev. Biol. 136, 154–163 (1989).

    Article  Google Scholar 

  15. Wetts, R. & Fraser, S. E. Multipotent precursors can give rise to all major cell types in the frog retina. Science 239, 1142–1145 (1988).

    CAS  Article  Google Scholar 

  16. Younossi-Hartenstein, A., Tepass, U. & Hartenstein, V. Embryonic origin of the imaginal discs of the head of Drosophila melanogaster. Wilhelm Roux Arch. Dev. Biol. 203, 60–73 (1993).

    Article  Google Scholar 

  17. Campos-Ortega, J. A. & Hartenstein, V. The Embryonic Development of Drosophila melanogaster (Springer, Berlin, (1985)).

    Book  Google Scholar 

  18. Sakaguchi, D. A. Neurosci. Abstr. 16, 479.5 (1990).

    Google Scholar 

  19. Huang, S. & Moody, S. A. The retinal fate of Xenopus cleavage stage progenitors is dependent upon blastomere position and competence: Studies of normal and regulated clones. J. Neurosci. 13, 3193–3210 (1993).

    CAS  Article  Google Scholar 

  20. Hogan, B. L. M. et al. Small eye(Sey): a homozygous lethal mutation on chromosome 2 which affects the differentiation of both lens and nasal placodes in the mouse. J. Embryol. Exp. Morphol. 97, 95–110 (1986).

    CAS  PubMed  Google Scholar 

  21. Grindley, J. C., Davidson, D. R. & Hill, R. E. The role of Pax-6 in eye and nasal development. Development 121, 1433–1442 (1995).

    CAS  PubMed  Google Scholar 

  22. Richter, K., Grunz, H. & Dawid, I. B. Gene expression in the embryonic nervous system of Xenopus laevis. Proc. Natl Acad. Sci. USA 85, 8086–8090 (.1988).

    CAS  Article  Google Scholar 

  23. Nieuwkoop, P. D. & Faber, J. Normal table of Xenopus laevis (Daudin), 2nd edn (North-Holland, Amsterdam, (1967)).

    Google Scholar 

  24. Harland, R. M. In situ hybridization: An improved whole-mount method for Xenopus embryos. Methods Cell Biol. 36, 685–695 (1991).

    CAS  Article  Google Scholar 

  25. Conlon, R. A. & Rossant, J. Exogenous retinoic acid rapidly induces anterior ectopic expression of murine Hox2 genes in vivo. Development 116, 357–368 (1992).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank M.-L. Dirksen, K. T. Ault, N. Papalopulu, M. Whiteley, J. Kassis, F. D. Porter, D. Feltner, D. Sakaguchi, S. Witta, M. Moos, I. Dawid, S. Moody, T. Sargent, G. Spirou, A. Berrebi and O.Sundin for materials and advice.

Author information

Author notes

  1. K. A. Mahon

    Present address: Department of Cell Biology, Baylor College of Medicine, Houston, 77030, Texas, USA

  2. P. H. Mathers

    Present address: Departments of Otolaryngology and Biochemistry, West Virginia University School of Medicine, Morgantown, West Virginia, 26506, USA

Authors and Affiliations

  1. Laboratory of Developmental Biology, Food and Drug Administration, Rockville, 20852, Maryland, USA

    P. H. Mathers & M. Jamrich

  2. Laboratory of Mammalian Genes and Development, NICHD, NIH, Bethesda, 20892, Maryland, USA

    A. Grinberg

Authors
  1. P. H. Mathers
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Grinberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K. A. Mahon
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Jamrich
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. Jamrich.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Mathers, P., Grinberg, A., Mahon, K. et al. The Rx homeobox gene is essential for vertebrate eye development. Nature 387, 603–607 (1997). https://doi.org/10.1038/42475

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/42475

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

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