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GLI-Kruppel family member GLI3 (Greig cephalopolysyndactyly syndrome)
External IDs OMIM165240 MGI95729 HomoloGene139 GeneCards: GLI3 Gene
RNA expression pattern
PBB GE GLI3 205201 at tn.png
More reference expression data
Species Human Mouse
Entrez 2737 14634
Ensembl ENSG00000106571 ENSMUSG00000021318
UniProt P10071 Q3TYX7
RefSeq (mRNA) NM_000168 NM_008130
RefSeq (protein) NP_000159 NP_032156
Location (UCSC) Chr 7:
41.97 - 42.23 Mb
Chr 13:
15.25 - 15.52 Mb
PubMed search [1] [2]

Zinc finger protein GLI3 is a protein that in humans is encoded by the GLI3 gene.[1][2]

This gene encodes a protein which belongs to the C2H2-type zinc finger proteins subclass of the Gli family. They are characterized as DNA-binding transcription factors and are mediators of Sonic hedgehog (Shh) signaling. The protein encoded by this gene localizes in the cytoplasm and activates patched Drosophila homolog (PTCH1) gene expression. It is also thought to play a role during embryogenesis.[2]


Role in development

Gli3 is a known transcriptional repressor but may also have a positive transcriptional function.[3][4] Gli3 represses dHand and Gremlin which are involved in developing digits.[5] 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.[6][7][8][9]

Disease association

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.[2]

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.[10]

Interactions with Gli1 and Gli2

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.[11]

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.


GLI3 has been shown to interact with ZIC1,[12] CREB binding protein[13] and ZIC2.[12]


  1. ^ Ruppert JM, Vogelstein B, Arheden K, Kinzler KW (Oct 1990). "GLI3 encodes a 190-kilodalton protein with multiple regions of GLI similarity". Mol Cell Biol 10 (10): 5408–15. PMID 2118997.  
  2. ^ a b c "Entrez Gene: GLI3 GLI-Kruppel family member GLI3 (Greig cephalopolysyndactyly syndrome)".  
  3. ^ Taipale J, Beachy PA (2001). "The Hedgehog and Wnt signalling pathways in cancer". Nature 411 (6835): 349–54. doi:10.1038/35077219. PMID 11357142.  
  4. ^ a b Jacob J, Briscoe J (2003). "Gli proteins and the control of spinal-cord patterning". EMBO Rep. 4 (8): 761–5. doi:10.1038/sj.embor.embor896. PMID 12897799.  
  5. ^ te Welscher P, Fernandez-Teran M, Ros MA, Zeller R (2002). "Mutual genetic antagonism involving GLI3 and dHAND prepatterns the vertebrate limb bud mesenchyme prior to SHH signaling". Genes Dev. 16 (4): 421–6. doi:10.1101/gad.219202. PMID 11850405.  
  6. ^ Franz T (1994). "Extra-toes (Xt) homozygous mutant mice demonstrate a role for the Gli-3 gene in the development of the forebrain". Acta Anat (Basel) 150 (1): 38–44. doi:10.1159/000147600. PMID 7976186.  
  7. ^ Grove EA, Tole S, Limon J, Yip L, Ragsdale CW (1998). "The hem of the embryonic cerebral cortex is defined by the expression of multiple Wnt genes and is compromised in Gli3-deficient mice". Development 125 (12): 2315–25. PMID 9584130.  
  8. ^ Hui CC, Joyner AL (1993). "A mouse model of greig cephalopolysyndactyly syndrome: the extra-toesJ mutation contains an intragenic deletion of the Gli3 gene". Nat. Genet. 3 (3): 241–6. doi:10.1038/ng0393-241. PMID 8387379.  
  9. ^ Schimmang T, Lemaistre M, Vortkamp A, Rüther U (1992). "Expression of the zinc finger gene Gli3 is affected in the morphogenetic mouse mutant extra-toes (Xt)". Development 116 (3): 799–804. PMID 1289066.  
  10. ^ Böse J, Grotewold L, Rüther U (2002). "Pallister-Hall syndrome phenotype in mice mutant for Gli3". Hum. Mol. Genet. 11 (9): 1129–35. doi:10.1093/hmg/11.9.1129. PMID 11978771.  
  11. ^ Dahmane N, Lee J, Robins P, Heller P, Ruiz i Altaba A (1997). "Activation of the transcription factor Gli1 and the Sonic hedgehog signalling pathway in skin tumours". Nature 389 (6653): 876–81. doi:10.1038/39918. PMID 9349822.  
  12. ^ a b Koyabu, Y; Nakata K, Mizugishi K, Aruga J, Mikoshiba K (Mar. 2001). "Physical and functional interactions between Zic and Gli proteins". J. Biol. Chem. (United States) 276 (10): 6889–92. doi:10.1074/jbc.C000773200. ISSN 0021-9258. PMID 11238441.  
  13. ^ Dai, P; Akimaru H, Tanaka Y, Maekawa T, Nakafuku M, Ishii S (Mar. 1999). "Sonic Hedgehog-induced activation of the Gli1 promoter is mediated by GLI3". J. Biol. Chem. (UNITED STATES) 274 (12): 8143–52. ISSN 0021-9258. PMID 10075717.  

External links

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



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