A trophic role for Wnt-Ror kinase signaling during developmental pruning in Caenorhabditis elegans.
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.
Hayashi
Yu
Y
Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo, Japan. yuhayashi@brain.riken.jp <yuhayashi@brain.riken.jp>
Hirotsu
Takaaki
T
Iwata
Ryo
R
Kage-Nakadai
Eriko
E
Kunitomo
Hirofumi
H
Ishihara
Takeshi
T
Iino
Yuichi
Y
Kubo
Takeo
T
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D017173:Caenorhabditis elegans / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D009154:Mutation / Q000502:physiology; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D009420:Nervous System / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development*; D016501:Neurites / Q000201:enzymology / Q000648:ultrastructure; D055495:Neurogenesis / Q000502:physiology; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D051155:Wnt1 Protein / Q000235:genetics / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; C508848:MBR-1 protein, C elegans; D009414:Nerve Growth Factors; D014157:Transcription Factors; D051155:Wnt1 Protein; C526267:CAM-1 protein, C elegans; D020794:Receptor Protein-Tyrosine Kinases; D057050:Receptor Tyrosine Kinase-like Orphan Receptors