Wnt signaling is required for thymocyte development and   activates Tcf-1 mediated transcription.
T cell factor / lymphocyte enhancer factor (Tcf/Lef) transcription factors complex with the transcriptional co-activator beta-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 beta-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.
Department of Immunology and Center for Biomedical Genetics, Utrecht Medical Center, Utrecht, The Netherlands.
F J
FJ
Staal
J
J
Meeldijk
P
P
Moerer
P
P
Jay
B C
BC
van de Weerdt
S
S
Vainio
G P
GP
Nolan
H
H
Clevers
D000818:Animals; D003598:Cytoskeletal Proteins / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology*; D051538:Hepatocyte Nuclear Factor 1-alpha; D051821:Lymphoid Enhancer-Binding Factor 1; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D015398:Signal Transduction; D051822:T Cell Transcription Factor 1; D013601:T-Lymphocytes / Q000502:physiology*; D015534:Trans-Activators; D014157:Transcription Factors / Q000502:physiology*; D015533:Transcriptional Activation; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D051538:Hepatocyte Nuclear Factor 1-alpha; C496488:Hnf1a protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D011518:Proto-Oncogene Proteins; D051822:T Cell Transcription Factor 1; D015534:Trans-Activators; D014157:Transcription Factors; D051153:Wnt Proteins; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; D029961:Zebrafish Proteins; D051176:beta Catenin