The involvement of Frodo in TCF-dependent signaling and neural tissue development.
Frodo is a novel conserved regulator of Wnt signaling that has been identified by its association with Dishevelled, an intracellular component of Wnt signal transduction. To understand further how Frodo functions, we have analyzed its role in neural development using specific morpholino antisense oligonucleotides. We show that Frodo and the closely related Dapper synergistically regulate head development and morphogenesis. Both genes were cell-autonomously required for neural tissue formation, as defined by the pan-neural markers sox2 and nrp1. By contrast, beta-catenin was not required for pan-neural marker expression, but was involved in the control of the anteroposterior patterning. In the mesoderm, Frodo and Dapper were essential for the expression of the organizer genes chordin, cerberus and Xnr3, but they were not necessary for the expression of siamois and goosecoid, established targets of beta-catenin signaling. Embryos depleted of either gene showed a decreased transcriptional response to TCF3-VP16, a beta-catenin-independent transcriptional activator. Whereas the C terminus of Frodo binds Dishevelled, we demonstrate that the conserved N-terminal domain associates with TCF3. Based on these observations, we propose that Frodo and Dapper link Dsh and TCF to regulate Wnt target genes in a pathway parallel to that of beta-catenin.
Department of Microbiology and Molecular Genetics, Harvard Medical School, and Department of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA.
Hiroki
H
Hikasa
Sergei Y
SY
Sokol
D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D002352:Carrier Proteins / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000502:physiology; D018076:DNA, Complementary / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D024002:HMGB Proteins / Q000502:physiology*; D009417:Nerve Tissue / Q000196:embryology*; D015398:Signal Transduction; D051820:TCF Transcription Factors; D015534:Trans-Activators / Q000502:physiology; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors / Q000502:physiology*; D014981:Xenopus / Q000196:embryology / Q000235:genetics / Q000502:physiology; D029867:Xenopus Proteins / Q000502:physiology*; D051176:beta Catenin
D048868:Adaptor Proteins, Signal Transducing; C495266:CTNNB1 protein, Xenopus; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C454443:DACT1 protein, Xenopus; D018076:DNA, Complementary; D024002:HMGB Proteins; D051820:TCF Transcription Factors; D015534:Trans-Activators; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors; D029867:Xenopus Proteins; D051176:beta Catenin