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Autocrine/juxtaparacrine regulation of axon fasciculation by Slit-Robo signaling

Nature Neuroscience volume 15, pages 367–369 (2012)Cite this article

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Abstract

Axons travel to their targets in bundles or fascicles, but the molecules regulating fasciculation remain incompletely characterized. We found that Slit2 and its Robo receptors are expressed by motor axons, and that inactivation of Slit2 or Robo1 and Robo2 in mice caused axons to defasciculate prematurely at muscle targets. In vitro, Slit2 secreted by motoneurons regulated fasciculation through Robo1 and Robo2. These results support the idea that Slit2 promotes axon fasciculation via an autocrine and/or juxtaparacrine mechanism.

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Figure 1: Motor axons prematurely defasciculate during muscle innervation in mice lacking either Slit2 or Robo1 and Robo2.
Figure 2: Slit2 regulates motor axon fasciculation through Robo1 and Robo2 in vitro.
Figure 3: Motoneuron-derived Slit2 regulates fasciculation in vitro.

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Acknowledgements

We thank N. Velarde for technical assistance, A. Koch and colleagues (Genentech) for expression and purification of Slit2, Robo1-Fc and Robo1-AP, S. Pfaff (Salk Institute) and J. Lewcock (Genentech) for sharing the HB9 antibody, and D. Simon for thoughtful comments on the manuscript. This work was supported by Genentech and The Rockefeller University.

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Authors and Affiliations

  1. Division of Research, Genentech, South San Francisco, California, USA

    Alexander Jaworski & Marc Tessier-Lavigne

  2. Laboratory of Brain Development and Repair, Rockefeller University, New York, New York, USA

    Alexander Jaworski & Marc Tessier-Lavigne

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  1. Alexander Jaworski
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  2. Marc Tessier-Lavigne
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Contributions

A.J. carried out all experiments, with the exception of those listed in the Acknowledgments, and wrote the paper. M.T.-L. supervised all of the experiments and wrote the paper.

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Correspondence to Marc Tessier-Lavigne.

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The authors declare no competing financial interests.

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Jaworski, A., Tessier-Lavigne, M. Autocrine/juxtaparacrine regulation of axon fasciculation by Slit-Robo signaling. Nat Neurosci 15, 367–369 (2012). https://doi.org/10.1038/nn.3037

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