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RGM is a repulsive guidance molecule for retinal axons

Nature volume 419, pages 392–395 (2002)Cite this article

Abstract

Axons rely on guidance cues to reach remote targets during nervous system development1. A well-studied model system for axon guidance is the retinotectal projection. The retina can be divided into halves; the nasal half, next to the nose, and the temporal half. A subset of retinal axons, those from the temporal half, is guided by repulsive cues expressed in a graded fashion in the optic tectum2,3, part of the midbrain. Here we report the cloning and functional characterization of a membrane-associated glycoprotein, which we call RGM (repulsive guidance molecule). This molecule shares no sequence homology with known guidance cues, and its messenger RNA is distributed in a gradient with increasing concentration from the anterior to posterior pole of the embryonic tectum. Recombinant RGM at low nanomolar concentration induces collapse of temporal but not of nasal growth cones and guides temporal retinal axons in vitro, demonstrating its repulsive and axon-specific guiding activity.

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Figure 1: RGM sequence, domain model, and hydrophobicity profile.
Figure 2: Graded expression of RGM in the embryonic optic tectum.
Figure 3: Collapse of temporal retinal growth cones induced by RGM.
Figure 4: Guidance of temporal retinal axons by RGM.

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References

  1. Yu, T. W. & Bargmann, C. I. Dynamic regulation of axon guidance. Nature Neurosci. 4, 1169–1176 (2001)

    Article  CAS  PubMed  Google Scholar 

  2. Walter, J. et al. Recognition of position-specific properties of tectal cell membranes by retinal axons in vitro. Development 101, 685–696 (1987)

    CAS  PubMed  Google Scholar 

  3. Walter, J., Müller, B. & Bonhoeffer, F. Axonal guidance by an avoidance mechanism. J. Physiol. (Paris) 84, 104–110 (1990)

    CAS  Google Scholar 

  4. Cheng, H. J. et al. Complementary gradients in expression and binding of ELF-1 and Mek4 in development of the topographic retinotectal projection map. Cell 82, 371–381 (1995)

    Article  CAS  PubMed  Google Scholar 

  5. Drescher, U. et al. In vitro guidance of retinal ganglion cell axons by RAGS, a 25 kDa tectal protein related to ligands for Eph receptor tyrosine kinases. Cell 82, 359–370 (1995)

    Article  CAS  PubMed  Google Scholar 

  6. Stahl, B. et al. Biochemical characterization of a putative axonal guidance molecule of the chick visual system. Neuron 5, 735–743 (1990)

    Article  CAS  PubMed  Google Scholar 

  7. Kozak, M. An analysis of 5′-noncoding sequences from 699 vertebrate messenger RNAs. Nucleic Acids Res. 15, 8125–8148 (1987)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Kyte, J. & Doolittle, R. F. A simple method for displaying the hydropathic character of a protein. J. Mol. Biol. 157, 105–132 (1982)

    Article  CAS  PubMed  Google Scholar 

  9. Ruoslahti, E. RGD and other recognition sequences for integrins. Annu. Rev. Cell Dev. Biol. 12, 697–715 (1996)

    Article  CAS  PubMed  Google Scholar 

  10. Sadler, J. E. Biochemistry and genetics of von Willebrand factor. Annu. Rev. Biochem. 67, 395–424 (1998)

    Article  CAS  PubMed  Google Scholar 

  11. Rathjen, F. G. et al. Membrane glycoproteins involved in neurite fasciculation. J. Cell Biol. 104, 343–353 (1987)

    Article  CAS  PubMed  Google Scholar 

  12. Cox, E. C., Müller, B. & Bonhoeffer, F. Axonal guidance in the chick visual system: posterior tectal membranes induce collapse of growth cones from the temporal retina. Neuron 4, 31–37 (1990)

    Article  CAS  PubMed  Google Scholar 

  13. Baier, H. & Bonhoeffer, F. Axon guidance by gradients of a target-derived component. Science 255, 472–475 (1992)

    Article  ADS  CAS  PubMed  Google Scholar 

  14. Wilm, M. et al. Femtomole sequencing of proteins from polyacrylamide gels by nanoelectrospray mass spectrometry. Nature 379, 466–469 (1996)

    Article  ADS  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank P. Sonderegger for providing an embryonic chicken cDNA library, F. Rathjen for antibodies, H. Pachowsky for technical help; and S. Arber and B. Fackler for comments and suggestions. This work was supported by the Sonderforschungsbereich (B.K.M.) and the Danish National Research Foundation (M.M.).

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Author notes

  1. Philippe P. Monnier, Ana Sierra and Manuela Flad: These authors contributed equally to this work

Authors and Affiliations

  1. Migragen AG, Spemannstraße 34, 72076, Tuebingen, Germany

    Philippe P. Monnier, Ana Sierra, Lutz Deitinghoff, Martin R. Hornberger, Bernd Stahl & Bernhard K. Mueller

  2. Max-Planck-Institut für Entwicklungsbiologie, Spemannstraße 35, 72076, Tuebingen, Germany

    Paolo Macchi & Friedrich Bonhoeffer

  3. Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, 5230 M, Odense, Denmark

    Jens S. Andersen & Matthias Mann

  4. DeveloGen AG, 37079, Goettingen, Germany

    Manuela Flad

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  1. Philippe P. Monnier
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Correspondence to Bernhard K. Mueller.

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Monnier, P., Sierra, A., Macchi, P. et al. RGM is a repulsive guidance molecule for retinal axons. Nature 419, 392–395 (2002). https://doi.org/10.1038/nature01041

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