Regulation of TCF3 Phosphorylation and Function by Wnt Signaling Center for Developmental Biology

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Category	Seminar
Date and Time	2009-06-04 16:00 - 17:00
Venue	Auditorium C1F
Speaker	Hiroki Hikasa
Affiliation	Mount Sinai School Of Medicine, Department of Developmental and Regenerative Biology
Title	Regulation of TCF3 Phosphorylation and Function by Wnt Signaling
Poster	click here to download(PDF)
Host	Hiroshi Sasaki
Summary	T-cell factor 3 (TCF3) plays key roles in cell fate determination in vertebrate embryos and embryonic stem cell differentiation and has been implicated in Wnt signaling. Based on genetic evidence and knockdown experiments, vertebrate TCF3 proteins function largely as transcriptional repressors, although the mechanism of TCF3 regulation and function remains unclear. A commonly accepted model of Wnt signaling in Drosophila and mammalian cells involves target gene activation by a complex of a TCF family member with beta-catenin. Here we demonstrate that Wnt proteins stimulate rapid phosphorylation of TCF3 in Xenopus gastrulae and mouse embryonic stem cells. This phosphorylation event is essential for maintaining ventroposterior fate, involves homeodomain-interacting protein kinase 2 (HIPK2) and beta-catenin and leads to the dissociation of TCF3 from the promoter of Vent2, a Wnt target gene with a pivotal role in ventroposterior development. These results reveal a novel Wnt signaling mechanism operating to control cell fates in vertebrate embryogenesis.