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Robo2-Slit1 dependent cell-cell interactions mediate assembly of the trigeminal ganglion

Nature Neuroscience volume 11, pages 269–276 (2008)Cite this article

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Abstract

Vertebrate cranial sensory ganglia, responsible for sensation of touch, taste and pain in the face and viscera, are composed of both ectodermal placode and neural crest cells. The cellular and molecular interactions allowing generation of complex ganglia remain unknown. Here, we show that proper formation of the trigeminal ganglion, the largest of the cranial ganglia, relies on reciprocal interactions between placode and neural crest cells in chick, as removal of either population resulted in severe defects. We demonstrate that ingressing placode cells express the Robo2 receptor and early migrating cranial neural crest cells express its cognate ligand Slit1. Perturbation of this receptor-ligand interaction by blocking Robo2 function or depleting either Robo2 or Slit1 using RNA interference disrupted proper ganglion formation. The resultant disorganization mimics the effects of neural crest ablation. Thus, our data reveal a novel and essential role for Robo2-Slit1 signaling in mediating neural crest–placode interactions during trigeminal gangliogenesis.

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Figure 1: Placode and neural crest cells are in contact during trigeminal gangliogenesis.
Figure 2: Expression of Robo2 mRNA in placode and Slit1 mRNA in neural crest cells during early development of the trigeminal ganglion.
Figure 3: Proper formation of the trigeminal ganglion relies on reciprocal interactions between placode and neural crest.
Figure 4: Inhibition of Robo2 signaling disrupts trigeminal ganglion formation.
Figure 5: Inhibition of Robo2 signaling disrupts the ingression of trigeminal placode cells.
Figure 6: Inhibition of Robo2 signaling disrupts neural crest aggregation into the trigeminal ganglion.
Figure 7: RNAi-mediated knockdown of Robo2 or its ligand Slit1 causes abnormal trigeminal ganglion assembly.

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Change history

  • 24 February 2008

    In the version of this article initially published, panel d was mistakenly listed in the legend of Figure 1 as x400 magnification. The correct panel should be c. The error has been corrected in the HTML and PDF versions of the article.

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Acknowledgements

We thank S. Guthrie for the Robo2Δ-GFP plasmid, members of the M.B.-F. lab for technical support, and S. Fraser, D. Meulemans and T. Hochgreb for comments on the manuscript. This work was supported by US National Institutes of Health (NIH) National Research Service Award 5T32 GM07616 to C.E.S., NIH Minority Supplement grant DE016459-07S1 to P.Y.L., a UK Biotechnology and Biological Sciences Research Council grant to R.M.D. and NIH grant DE16459 to M.B.-F.

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Authors and Affiliations

  1. Division of Biology 139-74, California Institute of Technology, Pasadena, 91125, California, USA

    Celia E Shiau, Peter Y Lwigale & Marianne Bronner-Fraser

  2. Department of Molecular Biology and Biotechnology, The University of Sheffield, Firth Court, Western Bank, Sheffield, S10 2TN, UK

    Raman M Das & Stuart A Wilson

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  1. Celia E Shiau
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Contributions

C.E.S. conducted all the experiments with help from P.Y.L. on the ablation and grafting experiments. C.E.S. designed the experiments and evaluated the data with contributions from P.Y.L. and M.B.-F. R.M.D. and S.A.W. designed and provided the RNAi reagents. C.E.S., P.Y.L. and M.B.-F. wrote the manuscript.

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Correspondence to Marianne Bronner-Fraser.

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Shiau, C., Lwigale, P., Das, R. et al. Robo2-Slit1 dependent cell-cell interactions mediate assembly of the trigeminal ganglion. Nat Neurosci 11, 269–276 (2008). https://doi.org/10.1038/nn2051

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