The C. elegans Frizzled CFZ-2 is required for cell migration and interacts with multiple Wnt signaling pathways.
Members of the Frizzled family of integral membrane proteins are implicated in many developmental events, including specifying cell fate, orienting cell and planar polarity, and directing cell migration. Frizzleds function as cell surface receptors for secreted Wnt proteins. We report here the isolation of a mutation in cfz-2, a Caenorhabditis elegans Frizzled gene. Mutation of cfz-2 causes defective cell migration, disorganization of head neurons, and can cause ectopic axon outgrowth. Analysis of mosaic animals shows that CFZ-2 functions cell nonautonomously, but does not rule out an autonomous role. CFZ-2 is expressed primarily in the anterior of embryos and in several cells in the head of adults. Our analysis of interactions between CFZ-2 and other Wnt pathways reveals that three Wnts, CWN-1, CWN-2 and EGL-20, and a Frizzled, MOM-5, function redundantly with one another and with CFZ-2 for specific cell migrations. In contrast, CWN-1, CWN-2, EGL-20, CFZ-2, and MOM-5 antagonize one another for other migrations. Therefore, CFZ-2 functions by collaborating with and/or antagonizing other Wnt signaling pathways to regulate specific cell migrations.
Zinovyeva
Anna Y
AY
Department of Biology, Indiana University, Bloomington, IN 47405, USA.
Forrester
Wayne C
WC
D000595:Amino Acid Sequence; D000704:Analysis of Variance; D000818:Animals; D001369:Axons / Q000502:physiology; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D017931:DNA Primers; D051157:Frizzled Receptors / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D051153:Wnt Proteins / Q000378:metabolism*
C554443:CFZ-2 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D017931:DNA Primers; D051157:Frizzled Receptors; D051153:Wnt Proteins