Wnt signaling is required for thymocyte development and activates Tcf-1 mediated transcription

Frank J.T. Staal, Jan Meeldijk, Petra Moerer, Philippe Jay, Barbara C.M. van de Weerdt, Seppo Vainio, Garry P. Nolan, Hans Clevers

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

165 Citaten (Scopus)

Samenvatting

T cell factor/lymphocyte enhancer factor (Tcf/Lef) transcription factors complex with the transcriptional co-activator β-catenin to transduce Wnt signals in a variety of developmental systems. The prototypic family member Tcf-1 is highly expressed in T lineage cells. Tcf1-/- mice are defective in cell cycling of early thymocyte stages. Here, we show that the interaction of β-catenin with Tcf-1 is required for full thymocyte development. This interaction may be established by signals mediated by Wnt1 and Wnt4, leading to increased Tcf-dependent transcriptional activity in thymocytes, as demonstrated in Tcf-LacZ reporter mice. Transduction of fetal thymocytes with Wnt1 and Wnt4 results in increased survival in an in vitro cell culture system. Retroviral expression of soluble Wnt receptor mutants that block Wnt signaling inhibits thymocyte development. These results imply an important role for the Wnt cascade in thymocyte development.

Originele taal-2Engels
Pagina's (van-tot)285-293
Aantal pagina's9
TijdschriftEuropean Journal of Immunology
Volume31
Nummer van het tijdschrift1
DOI's
StatusGepubliceerd - 2001
Extern gepubliceerdJa

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