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Dev Biol 2012 Jan 15;3612:220-31. doi: 10.1016/j.ydbio.2011.10.026.
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Xenopus Zic3 controls notochord and organizer development through suppression of the Wnt/β-catenin signaling pathway.

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.

PubMed ID: 22056782
Article link: Dev Biol

Species referenced: Xenopus laevis
Genes referenced: actl6a acvr1 cat.2 ctnnb1 dvl1 gal.2 gsc hoxb9 hoxc9-like mdfic myc nodal3.1 not sia1 sia2 tbx2 tbxt tcf7 zic1 zic2 zic3 zic4 zic5
Antibodies: Ctnnb1 Ab2
Morpholinos: zic2 MO1 zic3 MO1

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