T-Cell factor 4 (tcf7l2) is the main effector of Wnt signaling during zebrafish intestine organogenesis

Ana Faro, Sylvia F. Boj, Raquel Ambrósio, Olaf Van Den Broek, Jeroen Korving, Hans Clevers

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

18 Citaten (Scopus)


The Wnt pathway orchestrates cell fate decisions during embryonic development, organogenesis, and adult tissues homeostasis. T-cell factor (Tcf)/lymphoid enhancer-binding factor (Lef) transcription factors are the downstream effectors of canonical Wnt signaling. Upon Wnt signal activation, β-catenin stabilizes and translocates to the nucleus, where it interacts with Tcfs activating the transcription of Wnt target genes. In the absence of Wnt, levels of stable β-catenin are reduced by the action of adenomatous polyposis coli (Apc) and other cytoplasmic proteins. Mutations in Apc cause constitutive accumulation of β-catenin and inappropriate activation of the Wnt pathway. apcmcr/mcr fish embryos show absence of expression of tissue-specific differentiation markers in the intestine, suggesting that inappropriate activation of Wnt signaling abrogates gut organogenesis. Which Tcf transcription factor mediates Wnt signaling during zebrafish gut organogenesis remains unclear. We studied the combined effect of loss of Tcf family members and Apc in the developing embryo. Tcf4 (tcf7l2) loss rescues the apc mcr/mcr phenotype in the intestine. Single depletion of Tcf1 (tcf7) and Tcf3 (tcf7l1a) function in an Apc mutant background had no effect on endoderm development. This study reveals that Tcf4 (tcf7l2) is the major effector of Wnt signaling in the intestine during zebrafish organogenesis.

Originele taal-2Engels
Pagina's (van-tot)59-68
Aantal pagina's10
Nummer van het tijdschrift1
StatusGepubliceerd - 1 mrt. 2009
Extern gepubliceerdJa


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