title: Xenopus Zic3 controls notochord and organizer development through suppression of the Wnt/β-catenin signaling pathway.
abstract: Zic3 controls neuroectodermal differentiation and left-right patterning in Xenopus laevis embryos. Here we demonstrate that Zic3 can suppress Wnt/β-catenin signaling and control development of the notochord and Spemann's organizer. When we overexpressed Zic3 by injecting its RNA into the dorsal marginal zone of 2-cell-stage embryos, the embryos lost mesodermal dorsal midline structures and showed reduced expression of organizer markers (Siamois and Goosecoid) and a notochord marker (Xnot). Co-injection of Siamois RNA partially rescued the reduction of Xnot expression caused by Zic3 overexpression. Because the expression of Siamois in the organizer region is controlled by Wnt/β-catenin signaling, we subsequently examined the functional interaction between Zic3 and Wnt signaling. Co-injection of Xenopus Zic RNAs and β-catenin RNA with a reporter responsive to the Wnt/β-catenin cascade indicated that Zic1, Zic2, Zic3, Zic4, and Zic5 can all suppress β-catenin-mediated transcriptional activation. In addition, co-injection of Zic3 RNA inhibited the secondary axis formation caused by ventral-side injection of β-catenin RNA in Xenopus embryos. Zic3-mediated Wnt/β-catenin signal suppression required the nuclear localization of Zic3, and involved the reduction of β-catenin nuclear transport and enhancement of β-catenin degradation. Furthermore, Zic3 co-precipitated with Tcf1 (a β-catenin co-factor) and XIC (I-mfa domain containing factor required for dorsoanterior development). The findings in this report produce a novel system for fine-tuning of Wnt/β-catenin signaling.
authors: Laboratory for Behavioral and Developmental Disorders, RIKEN Brain Science Institute, Wako-shi, Saitama 351-0198, Japan.
authors: Takahiko J
authors: TJ
authors: Fujimi
authors: Minoru
authors: M
authors: Hatayama
authors: Jun
authors: J
authors: Aruga
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D017930:Genes, Reporter / Q000235:genetics; D018398:Homeodomain Proteins / Q000378:metabolism*; D008954:Models, Biological; D009672:Notochord / Q000196:embryology* / Q000378:metabolism*; D020897:Organizers, Embryonic / Q000196:embryology* / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding; D021381:Protein Transport; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics; D060449:Wnt Signaling Pathway; D029867:Xenopus Proteins / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D018398:Homeodomain Proteins; D014157:Transcription Factors; D029867:Xenopus Proteins; C109036:Zic3 protein, Xenopus