Article abstract
Nature Neuroscience 12, 981 - 987 (2009)
Published online: 28 June 2009 | doi:10.1038/nn.2347
A trophic role for Wnt-Ror kinase signaling during developmental pruning in Caenorhabditis elegans
Yu Hayashi1,4, Takaaki Hirotsu2,5, Ryo Iwata3,5, Eriko Kage-Nakadai1,4, Hirofumi Kunitomo3, Takeshi Ishihara2, Yuichi Iino3 & Takeo Kubo1
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.
- Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
- Department of Biology, Graduate School of Science, Kyushu University, Fukuoka, Japan.
- Deparment of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
- Present address: Laboratory for Behavioral Genetics, RIKEN Brain Science Institute, Saitama, Japan (Y.H.), and Department of Physiology, Tokyo Women's Medical University School of Medicine, Shinjuku-ku, Tokyo, Japan (E.K.-N.).
- These authors contributed equally to this work.
Correspondence to: Yu Hayashi1,4 e-mail: yuhayashi@brain.riken.jp
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