Activation ofWnt signaling enhances self-renewal of mouse embryonic and neural stem/progenitor cells. In contrast, undifferentiated\nES cells show a very low level of endogenousWnt signaling, and ectopic activation ofWnt signaling has been shown to block\nneuronal differentiation. Therefore, it remains unclear whether or not endogenous Wnt/????-catenin signaling is necessary for selfrenewal\nor neuronal differentiation of ES cells.To investigate this,we examined the expression profiles ofWnt signaling components.\nExpression levels of Wnts known to induce ????-catenin were very low in undifferentiated ES cells. Stable ES cell lines which can\nmonitor endogenous activity of Wnt/????-catenin signaling suggest that Wnt signaling was very low in undifferentiated ES cells,\nwhereas it increased during embryonic body formation or neuronal differentiation. Interestingly, application of small molecules\nwhich can positively (BIO, GSK3???? inhibitor) or negatively (IWR-1-endo, Axin stabilizer) controlWnt/????-catenin signaling suggests\nthat activation of that signaling at different time periods had differential effects on neuronal differentiation of 46C ES cells. Further,\nChIP analysis suggested that ????-catenin/TCF1 complex directly regulated the expression of Sox1 during neuronal differentiation.\nOverall, our data suggest thatWnt/????-catenin signaling plays differential roles at different time points of neuronal differentiation.
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