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Inhibitory Gli3 Activity Negatively Regulates Wnt/  -Catenin Signaling Ulloa F. et al, Current Biology (2007)

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1 Inhibitory Gli3 Activity Negatively Regulates Wnt/  -Catenin Signaling Ulloa F. et al, Current Biology (2007)

2 Hedgehog Signaling Varjosalo M. and Taipale J. JCS (2007) Development –Nervous System Disease –Cyclopia –Holoprosencephaly Cancer Homologes of Hedgehog –Sonic hedgehog –Indian hedgehog –Desert hedgehog

3 Shh Wnt1 Fuccillo et al. Nature Reviews Neuroscience (2006) Sonic Hedgehog in the Neural Tube Ventral Dorsal Proliferation and Survival of Neural Progenitors

4 Failure of a medulloblastoma-derived mutant of SUFU to suppress WNT signaling. - Taylor MD. et al, Oncogene (2004) Shifted, the Drosophila ortholog of Wnt inhibitory factor-1, controls the distribution and movement of Hedgehog. - Glise B. et al, Dev Cell (2005) Suppressing Wnt signaling by the hedgehog pathway through sFRP-1. - He J. et al, JBC (2006) Wnt signaling inhibitors regulate the transcriptional response to morphogenetic Shh-Gli signaling in the neural tube. - Lei O. et al, Dev Cell (2006) Gli1 acts through Snail and E-cadherin to promote nuclear signaling by beta-catenin. - Li X. et al, Oncogene (2007) Hedgehog and Wnt Signaling

5 Wnt signaling is decreased in the absence of Shh signaling In Shh null embryos, apoptotic cells were detected in ventral and dorsal regions. Ptc1Δloop2 – a dominant active form inhibits Hh signaling

6 Gli3R Iinhibits Canonical Wnt Signaling

7 Gli3R Inhibits  -Catenin Activity

8 Gli3R Inhibits  -Catenin-Induced Secondary Axis Formation in Xenopus Embryos

9 Gli3R Interacts with  -Catenin

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11 Gli3R In the absence of Shh signaling, high levels of Gli3R act to inhibit Wnt signaling. Result sFRP-1(?)


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