A trophic role for Wnt-Ror kinase signaling during developmental pruning in Caenorhabditis elegans

Yu Hayashi; Takaaki Hirotsu; Ryo Iwata; Eriko Kage-Nakadai; Hirofumi Kunitomo; Takeshi Ishihara; Yuichi Iino; Takeo Kubo

doi:10.1038/nn.2347

A trophic role for Wnt-Ror kinase signaling during developmental pruning in Caenorhabditis elegans

Nat Neurosci. 2009 Aug;12(8):981-7. doi: 10.1038/nn.2347. Epub 2009 Jun 28.

Authors

Yu Hayashi¹, Takaaki Hirotsu, Ryo Iwata, Eriko Kage-Nakadai, Hirofumi Kunitomo, Takeshi Ishihara, Yuichi Iino, Takeo Kubo

Affiliation

¹ Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo, Japan. [email protected] <[email protected]>

PMID: 19561603
DOI: 10.1038/nn.2347

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis / physiology
Caenorhabditis elegans / cytology
Caenorhabditis elegans / enzymology*
Caenorhabditis elegans / growth & development*
Caenorhabditis elegans Proteins / genetics
Caenorhabditis elegans Proteins / metabolism*
Cell Differentiation / physiology
Cell Survival / physiology
Mutation / physiology
Nerve Growth Factors / genetics
Nerve Growth Factors / metabolism
Nervous System / cytology
Nervous System / enzymology*
Nervous System / growth & development*
Neurites / enzymology
Neurites / ultrastructure
Neurogenesis / physiology
Receptor Protein-Tyrosine Kinases / genetics
Receptor Protein-Tyrosine Kinases / metabolism*
Receptor Tyrosine Kinase-like Orphan Receptors
Signal Transduction / physiology
Transcription Factors / genetics
Transcription Factors / metabolism
Wnt1 Protein / genetics
Wnt1 Protein / metabolism*

Substances

Caenorhabditis elegans Proteins
MBR-1 protein, C elegans
Nerve Growth Factors
Transcription Factors
Wnt1 Protein
CAM-1 protein, C elegans
Receptor Protein-Tyrosine Kinases
Receptor Tyrosine Kinase-like Orphan Receptors