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Midline crossing and Slit responsiveness of commissural axons require USP33

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Abstract

Commissural axons cross the ventral midline of the neural tube in a Slit-dependent manner. The underlying molecular mechanisms remain unclear. We found that the deubiquitinating enzyme USP33 interacts with the Robo1 receptor. USP33 was essential for midline crossing by commissural axons and for their response to Slit. Our results reveal a previously unknown role for USP33 in vertebrate commissural axon guidance and in Slit signaling.

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Figure 1: USP33 interacts with Robo1.
Figure 2: USP33 is required for Slit-induced growth cone collapse in commissural neurons.
Figure 3: USP33 is required for commissural axons to cross the midline.

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Acknowledgements

We thank Y. Zou and F. Murakami for generously providing the Sema3F construct and the antibody to Robo1, respectively, M. Katakura for support during this work and X. Chen for excellent technical support. This work has been supported by the James S. McDonnell Foundation (grant JSMF 220020180 to J.Y.W.) and the US National Institutes of Health (grants CA114197 and CA107193 to J.Y.W.).

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Author notes

  1. Junichi Yuasa-Kawada and Mariko Kinoshita-Kawada: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Lurie Comprehensive Cancer Center, Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA

    Junichi Yuasa-Kawada, Mariko Kinoshita-Kawada & Jane Y Wu

  2. Department of Urology, University of Rochester Medical Center, Rochester, New York, USA

    Guan Wu

  3. Peking University School of Life Sciences, Beijing, China

    Yi Rao

Authors
  1. Junichi Yuasa-Kawada
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  2. Mariko Kinoshita-Kawada
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  3. Guan Wu
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  4. Yi Rao
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  5. Jane Y Wu
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Contributions

J.Y.-K. and M.K.-K. carried out the experiments. J.Y.-K., M.K.-K., J.Y.W. and Y.R. designed the experiments, analyzed the data and wrote the manuscript. G.W. provided the GFP-USP33 construct.

Corresponding authors

Correspondence to Yi Rao or Jane Y Wu.

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Supplementary Figures 1–8 and Supplementary Methods (PDF 4965 kb)

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Yuasa-Kawada, J., Kinoshita-Kawada, M., Wu, G. et al. Midline crossing and Slit responsiveness of commissural axons require USP33. Nat Neurosci 12, 1087–1089 (2009). https://doi.org/10.1038/nn.2382

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