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Defects in pathfinding by cranial neural crest cells in mice lacking the neuregulin receptor ErbB4

Nature Cell Biology volume 2, pages 103–109 (2000)Cite this article

Abstract

Mouse embryos with a loss-of-function mutation in the gene encoding the receptor tyrosine kinase ErbB4 exhibit misprojections of cranial sensory ganglion afferent axons. Here we analyse ErbB4-deficient mice, and find that morphological differences between wild-type and mutant cranial ganglia correlate with aberrant migration of a subpopulation of hindbrain-derived cranial neural crest cells within the paraxial mesenchyme environment. In transplantation experiments using new grafting techniques in cultured mouse embryos, we determine that this phenotype is non-cell-autonomous: wild-type and mutant neural crest cells both migrate in a pattern consistent with the host environment, deviating from their normal pathway only when transplanted into mutant embryos. ErbB4 signalling events within the hindbrain therefore provide patterning information to cranial paraxial mesenchyme that is essential for the proper migration of neural crest cells.

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Figure 1: Cranial ganglion abnormalities in ErbB4–/– embryos.
Figure 2: Neural crest cells and placode-derived cells contribute to the ErbB4–/– phenotype.
Figure 3: A subpopulation of r4-derived neural crest cells is misguided in ErbB4–/– embryos.
Figure 4: DiI labelling confirms that the migration of only r4-derived neural crest cells is affected in ErbB4–/– embryos.
Figure 5: Misguided r4-derived neural crest cells are a late-migrating subpopulation.
Figure 6: Environmental, not crest-intrinsic, cues control the misrouting of neural crest cells in ErbB4–/– embryos.

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Acknowledgements

We thank S. Tsoni for technical assistance; M. Dixon and B. Fritzsch for critically reviewing the manuscript; H. Tidcombe for valuable discussions; D.J. Anderson and Q. Ma for the gift of NeuroD, Neurogenin-1 and Neurogenin-2 plasmids; C. Goridis for the Phox2b plasmid; and M. Wegner for the Sox10 plasmid. P.T. was supported by EMBO and HFSP postdoctoral fellowships. This work was funded by Core MRC Programme support and an EEC Biotechnology Network grant (BIO4 CT-960378) to R.K.

Correspondence and requests for materials should be addressed to M.G.

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  1. Jon P. Golding and Paul Trainor: These authors contributed equally to this work

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  1. Division of Neurobiology, National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA , UK

    Jon P. Golding & Martin Gassmann

  2. Division of Developmental Neurobiology, National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA , UK

    Paul Trainor & Robb Krumlauf

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Correspondence to Martin Gassmann.

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Golding, J., Trainor, P., Krumlauf, R. et al. Defects in pathfinding by cranial neural crest cells in mice lacking the neuregulin receptor ErbB4. Nat Cell Biol 2, 103–109 (2000). https://doi.org/10.1038/35000058

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