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Dev Cell 2010 Oct 19;194:521-32. doi: 10.1016/j.devcel.2010.09.005.
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Regulation of TCF3 by Wnt-dependent phosphorylation during vertebrate axis specification.

Hikasa H , Ezan J , Itoh K , Li X , Klymkowsky MW , Sokol SY .

A commonly accepted model of Wnt/β-catenin signaling involves target gene activation by a complex of β-catenin with a T-cell factor (TCF) family member. TCF3 is a transcriptional repressor that has been implicated in Wnt signaling and plays key roles in embryonic axis specification and stem cell differentiation. Here we demonstrate that Wnt proteins stimulate TCF3 phosphorylation in gastrulating Xenopus embryos and mammalian cells. This phosphorylation event involves β-catenin-mediated recruitment of homeodomain-interacting protein kinase 2 (HIPK2) to TCF3 and culminates in the dissociation of TCF3 from a target gene promoter. Mutated TCF3 proteins resistant to Wnt-dependent phosphorylation function as constitutive inhibitors of Wnt-mediated activation of Vent2 and Cdx4 during anteroposterior axis specification. These findings reveal an alternative in vivo mechanism of Wnt signaling that involves TCF3 phosphorylation and subsequent derepression of target genes and link this molecular event to a specific developmental process.

PubMed ID: 20951344
PMC ID: PMC2963175
Article link: Dev Cell
Grant support: [+]

Species referenced: Xenopus
Genes referenced: cdx4 chrd ctnnb1 eef1a2 egr2 hes7.1 hesx1 hipk1 hipk2 meis3 myc otx2 rax tbx2 tcf3 tcf7l1 ventx2.2 wnt3a wnt8a
Morpholinos: ctnnb1 MO1 fgf8 MO1 hipk2 MO1 tcf7l1 MO1 wnt8a MO1

Article Images: [+] show captions
References [+] :
Arce, Diversity of LEF/TCF action in development and disease. 2006, Pubmed