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RGM is a repulsive guidance molecule for retinal axons

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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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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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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