Gli3 is a known transcriptional repressor but may also have a positive transcriptional function.^[1][2] Gli3 represses dHand and Germlin which are involved in developing digits^[3] There is evidence that Shh-controlled processing (e.g cleavage) regulates transcriptional activity of Gli3 similarly to that of CI.^[4] Gli3 mutant mice have many abnormalities including CNS and lung defects and limb polydactyly.^[5][6][7][8] There is evidence that the autosomal dominant disorder Greig cephalopolysyndactyly syndrome (GCPS) that affects limb and craniofacial development in humans is caused by a translocations within the GLI3 gene.^[9]

The independent overexpression Gli1 and Gli2 in mice models to lead to formation of basal cell carcinoma (BCC). Gli1 knockout is shown to lead to similar embryonic malformations as Gli1 overexpressions but not the formation of BCC's. Overexpression of Gli3 in transgenic mice and frogs does not lead to the development of BCC-like tumors and is not thought to play a role in tumor BCC formation.^[10]

Gli1 and Gli2 overexpression leads to BCC formation in mouse models and a one step model for tumour formation has been suggested in both cases. This also indicates that Gli1 and/or Gli2 overexpression is vital in BCC formation. Co-overexpression of Gli1 with Gli2 and Gli2 with Gli3 leads to transgenic mice malformations and death respectively but not the formation of BCC. This suggests that over expression of more that one Gli protein is not necessary for BCC formation.

References

1. ^ Taipale and Beachy, 2001f
2. ^ Jacob and Briscoe, 2003
3. ^ te et al., 2002
4. ^ Jacob and Briscoe, 2003
5. ^ Franz, 1994
6. ^ Grove et al., 1998
7. ^ Hui and Joyner, 1993
8. ^ Schimmang et al., 1992
9. ^ Bose et al., 2002
10. ^ Dahmane et al., 1997