Fig. 7
Working model of the feedback loop involving Wnt3/β-catenin/TCF and Sp5. Wnt/β-catenin signaling positively regulates Wnt3 expression via β-catenin stabilization as well as Sp5 expression. Head organizer activity is restricted by Sp5 that positively auto-regulates its own expression, likely by interacting with the β-catenin/TCF complex, but also represses the expression of Wnt3 through the Wnt3 repressor element. Depending on the level of Sp5 in a cell, Sp5 might also repress its own expression. This tight transcriptional control mechanism might then ensure a stable repression of the Wnt3 promoter. In the absence of Sp5, the repressing effect on the Wnt3 promoter is lost and Wnt3 is no longer restricted to the head organizer. The release of Wnt3 expression is sufficient to trigger multiple head formation in intact and regenerating conditions as well as in reaggregates
