The N- or C-terminal domains of DSH-2 can activate the C. elegans Wnt/beta-catenin asymmetry pathway.
Dishevelleds are modular proteins that lie at the crossroads of divergent Wnt signaling pathways. The DIX domain of dishevelleds modulates a beta-catenin destruction complex, and thereby mediates cell fate decisions through differential activation of Tcf transcription factors. The DEP domain of dishevelleds mediates planar polarity of cells within a sheet through regulation of actin modulators. In Caenorhabditis elegans asymmetric cell fate decisions are regulated by asymmetric localization of signaling components in a pathway termed the Wnt/beta-catenin asymmetry pathway. Which domain(s) of Disheveled regulate this pathway is unknown. We show that C. elegans embryos from dsh-2(or302) mutant mothers fail to successfully undergo morphogenesis, but transgenes containing either the DIX or the DEP domain of DSH-2 are sufficient to rescue the mutant phenotype. Embryos lacking zygotic function of SYS-1/beta-catenin, WRM-1/beta-catenin, or POP-1/Tcf show defects similar to dsh-2 mutants, including a loss of asymmetry in some cell fate decisions. Removal of two dishevelleds (dsh-2 and mig-5) leads to a global loss of POP-1 asymmetry, which can be rescued by addition of transgenes containing either the DIX or DEP domain of DSH-2. These results indicate that either the DIX or DEP domain of DSH-2 is capable of activating the Wnt/beta-catenin asymmetry pathway and regulating anterior-posterior fate decisions required for proper morphogenesis.
King
Ryan S
RS
Cellular and Molecular Biology Program, University of Wisconsin, USA.
Maiden
Stephanie L
SL
Hawkins
Nancy C
NC
Kidd
Ambrose R
AR
Kimble
Judith
J
Hardin
Jeff
J
Walston
Timothy D
TD
D000818:Animals; D030801:Animals, Genetically Modified; D019521:Body Patterning / Q000502:physiology; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D016764:Cell Polarity / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology; D000072261:Dishevelled Proteins; D004625:Embryo, Nonmammalian / Q000502:physiology; D006609:High Mobility Group Proteins / Q000502:physiology; D009154:Mutation; D017434:Protein Structure, Tertiary; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*; D051153:Wnt Proteins / Q000502:physiology*; D051176:beta Catenin / Q000502:physiology*
D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D000072261:Dishevelled Proteins; D006609:High Mobility Group Proteins; C502083:Sys-1 protein, C elegans; D014157:Transcription Factors; C120104:WRM-1 protein, C elegans; D051153:Wnt Proteins; D051176:beta Catenin; C505142:dsh-2 protein, C elegans; C096787:pop-1 protein, C elegans