GLI3

Gli3 is a known transcriptional repressor but may also have a positive transcriptional function.[7][8] Gli3 represses dHand and Gremlin, which are involved in developing digits.[9] There is evidence that Shh-controlled processing (e.g., cleavage) regulates transcriptional activity of Gli3 similarly to that of Ci.[8] Gli3 mutant mice have many abnormalities including CNS and lung defects and limb polydactyly.[10][11][12][13][14] In the developing mouse limb bud, Gli3 derepression predominately regulates Shh target genes.[15]

Mutations in this gene have been associated with several diseases, including Greig cephalopolysyndactyly syndrome, Pallister-Hall syndrome, preaxial polydactyly type IV, and postaxial polydactyly types A1 and B.[6] DNA copy-number alterations that contribute to increased conversion of the oncogenes Gli1–3 into transcriptional activators by the Hedgehog signaling pathway are included in a genome-wide pattern, which was found to be correlated with an astrocytoma patient's outcome.[16][17]

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.[18]

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 BCCs. 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.[19]

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 overexpression of more than one Gli protein is not necessary for BCC formation.

GLI3 has been shown to interact with CREBBP[20] SUFU,[21] ZIC1,[22] and ZIC2.[22]

• GeneReviews/NCBI/NIH/UW entry on Pallister-Hall Syndrome
• GeneReviews/NCBI/NIH/UW entry on Greig Cephalopolysyndactyly Syndrome
• GLI3+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.