dTcf antagonises Wingless signalling during the development and patterning of the wing in Drosophila

Department of Genetics, University of Cambridge, UK.
The International Journal of Developmental Biology (Impact Factor: 1.9). 11/2000; 44(7):749-56.
Source: PubMed


Members of the Tcf family of HMG box-containing transcriptional regulators mediate Wnt signalling in the nucleus. Current models suggest that in the absence of Wnt signalling, Tcf interacts with the repressor protein Groucho and suppresses the expression of Wnt targets. Wnt signalling leads to increases in the level of cytoplasmic beta catenin, which enters the nucleus, displaces Tcf from Groucho and leads to transcriptional activation. In order to test this model we have studied the effects of Drosophila Tcf (dTcf) on signalling by Wingless, a Drosophila member of the Wnt family. We show that overexpression of wild-type dTcf during the development and patterning of the wing antagonises Wingless signalling. Furthermore, increases in the concentration of Armadillo, the Drosophila homologue of beta catenin, do not appear to be sufficient to trigger the change from antagonism to activation. This leads us to suggest that the inactivation of the repressive activity of dTcf requires the activity of Wingless in a manner that is independent of Armadillo. We observe that a Groucho molecule devoid of the WD40 repeats can interact with dTcf and acts as a dominant repressor of Wingless signalling in vivo and in vitro. Coexpression of this molecule with dTcf however, does not lead to enhancement of the repressive effects of dTcf alone. This observation suggests that repression by dTcf might not simply be mediated by an interaction with Groucho but that dTcf may have an intrinsic repressive activity that has to be antagonised by Wingless signalling.

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    • "Genetic or chemical inhibition of GSK3 results in an increase in the cytosolic levels of β-catenin, which can enter the nucleus and, through an interaction with members of the Tcf family of transcription factors, can promote gene expression. However, the levels of β-catenin might not be diagnostic of its transcriptional activity (Fagotto et al., 1997; Guger and Gumbiner, 2000; Lawrence et al., 2000; Staal et al., 2002; Tolwinski et al., 2003; Fodde and Brabletz, 2007; Hendriksen et al., 2008) and this has led to the suggestion that there is a transcriptionally competent form of β-catenin that represents a small fraction of the total pool (Staal et al., 2002; Maher et al., 2010; Muñoz Descalzo et al., 2011). "
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    Development 03/2013; 140(6):1171-83. DOI:10.1242/dev.085654 · 6.46 Impact Factor
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    • "Inactivation of the Axin/APC based scaffold through the adaptor protein Dishevelled results in a rise of cytosolic levels of ß-catenin and its entry into the nucleus where it modulates transcription through an interaction with members of the Tcf family of DNA binding proteins [17] [18]. Although the mantra of Wnt signalling links directly the levels of cytosolic ß-catenin to its transcriptional function, there is abundant evidence that this association is weak [19] [20] [21] [22] [23] [24] [25]. These studies indicate that there are at least two pools of ß-catenin, a cytosolic and a transcriptionally competent, which are represented by different phosphoisoforms and might have different subcellular locations; the transcriptionally competent pool [21] represents less than 1% of the total ß-catenin [26]. "
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    Seminars in Cell and Developmental Biology 02/2012; 23(4):443-9. DOI:10.1016/j.semcdb.2012.01.012 · 6.27 Impact Factor
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    • "It has been broadly assumed that the key component of Wnt signalling is the stabilisation and subsequent rise in concentration of a cytoplasmic pool of ß-catenin (reviewed in [1]). However, there is evidence that the concentration of β-catenin alone is not a determinant of Wnt signalling [35], [58]–[61], and it is becoming increasingly clear that other factors, like nuclear shuttling and cytoplasmic tethering, affect the nuclear availability of ß-catenin, and thus its ability to interact with the transcriptional machinery [39], [62]. It is possible that the association of ß-catenin with E-Cadherin also influences its activity under steady state conditions, not only in pathological or overexpression situations. "
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