Abstract
The molecular mechanism by which neurites are selected for elimination or incorporation into the mature circuit during developmental pruning remains unknown. The trophic theory postulates that local cues provided by target or surrounding cells act to inhibit neurite elimination. However, no widely conserved factor mediating this trophic function has been identified. We found that the developmental survival of specific neurites in Caenorhabditis elegans largely depends on detection of the morphogen Wnt by the Ror kinase CAM-1, which is a transmembrane tyrosine kinase with a Frizzled domain. Mutations in Wnt genes or in cam-1 enhanced neurite elimination, whereas overexpression of cam-1 inhibited neurite elimination in a Wnt-dependent manner. Moreover, mutations in these genes counteracted the effect of a mutation in mbr-1, which encodes a transcription factor that promotes neurite elimination. These results reveal the trophic role of an atypical Wnt pathway and reinforce the classical model of developmental pruning.
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Acknowledgements
We thank the Caenorhabditis Genetics Center funded by the US National Institutes of Health National Center for Research Resources for nematode strains; M. Tomioka, K. Yamada and M. Matsuki for constructs and technical advice; A. Fire for vectors; C. Bargmann, A. Kuhara and I. Mori for information on constructs; O. Hobert for sharing unpublished results on neurite pruning; and E. Matsuzaka for technical assistance. This work was supported by the Program for Promotion of Basic Research Activities for Innovative Bioscience. Y.H. was the recipient of a Grant-in-Aid for Japan Society for the Promotion of Science Fellows.
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Y.H. designed and Y.H., R.I. and H.K. conducted the experiments on anatomical studies. Y.H., T.H. and E.K.-N. designed and conducted the experiments on behavioral studies. Y.H. wrote the manuscript. T.I., Y.I. and T.K. supervised the project.
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Hayashi, Y., Hirotsu, T., Iwata, R. et al. A trophic role for Wnt-Ror kinase signaling during developmental pruning in Caenorhabditis elegans. Nat Neurosci 12, 981–987 (2009). https://doi.org/10.1038/nn.2347
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DOI: https://doi.org/10.1038/nn.2347
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