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Gene Review

Gli1  -  GLI-Kruppel family member GLI1

Mus musculus

Synonyms: AV235269, Gli, Glioma-associated oncogene homolog, Zfp-5, Zfp5, ...
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Disease relevance of Gli1


High impact information on Gli1

  • Here we show that ectopic expression of the zinc-finger transcription factor Gli1 in the embryonic frog epidermis results in the development of tumours that express endogenous Gli1 [6].
  • Two Shh target genes, ptc itself and Gli, were derepressed in the ectoderm and mesoderm but not in the endoderm [7].
  • Thus, Shh-N signaling may result in dephosphorylation of a target factor that is required for activation of COUP-TFII-, Islet1-, and Gli response element-dependent gene expression [8].
  • Here we show that Gli is rapidly destroyed by the proteasome and that mouse basal cell carcinoma induction correlates with Gli protein accumulation [9].
  • MIM/BEG4, a Sonic hedgehog-responsive gene that potentiates Gli-dependent transcription [10].

Chemical compound and disease context of Gli1

  • Three of the ten Gli3 mutant mice treated with triparanol, which blocks hedgehog signalling upstream of the Gli transcription factors, developed synovial chondromatosis, compared with eight of ten control mice [11].

Biological context of Gli1

  • Homozygous ptc1 cells expressed high levels of ptc1-lacZ without Hh stimulation. ptc1-lacZ expression was dependent on cell density in ptc1 homozygotes and Hh-stimulated heterozygotes but was independent of density when Gli1 was used to activate ptc1-lacZ [12].
  • Additionally, overexpression of Gli1 induced target gene expression in Gli2(-/-)3(-/-) MEFs, while Shh stimulation did not [13].
  • These results demonstrate that Gli2 and Gli3 share common regulatory mechanisms and modulate Hedgehog target gene expression directly and independently while also regulating Gli1 expression, which in specific contexts, coordinately contributes to target gene activation [13].
  • Cyclopamine treatment reduced Gli1 expression by 61% and initiation of cauda sperm motility by 50% [14].
  • Although genetic epistasis experiments place IFT proteins downstream of the Hh receptor and upstream of the Gli transcription factors, the mechanism by which IFT regulates Gli function is unknown [15].

Anatomical context of Gli1

  • Ectopic application of Shh protein to mandibular mesenchyme induced the expression of Ptc and Gli1 [16].
  • Furthermore, expression of both copies of Gli1 in place of Gli2 does not disrupt spinal cord patterning, but does result in new gain-of-function defects that lead to lethality [17].
  • In frog embryos, Gli1 is expressed transiently in the prospective floor plate during gastrulation and in cells lateral to the midline during late gastrula and neurula stages [18].
  • Gli1 was localized primarily to the nucleus of both HeLa cells and the Shh-responsive cell line MNS-70; co-expression with mSu(fu) resulted in a striking increase in cytoplasmic Gli1 immunostaining [19].
  • In cultured fibroblasts, Gli1 was more potent than Gli2 at inducing cell transformation [1].

Associations of Gli1 with chemical compounds

  • Nuclear localization of Gli1 was increased in Shh-treated IBE cells, which was not affected by LY294002 [20].
  • Adriamycin disruption of the Shh-Gli pathway is associated with abnormalities of foregut development [21].

Physical interactions of Gli1

  • Different domains of Smo are involved in Ptc binding and activation of a Gli reporter construct [22].
  • A Gli-binding site located within the ES enhancer is required for enhancer activation by Shh signaling in transfected 3T3 cells and in epaxial somite progenitors in transgenic embryos [23].

Regulatory relationships of Gli1

  • Ptc represses expression of Hh target genes such as Gli1 and ptc1 itself [24].
  • In both mutants Gli2 expression pattern was not altered, whereas Gli1 expression was anteriorly up-regulated adjacent to the ectopic Shh domain [25].
  • At the onset of ductal morphogenesis in the developing prostate, Shh expression condenses at evaginations of urogenital sinus epithelium and activates Gli transcription factors in the adjacent mesenchyme [26].
  • Our results demonstrate that Gli1 is not required to induce Pdgfra expression during embryonic bone development, and are consistent with previous findings that Pdgfralpha and Hh pathways serve different functions in, e.g., bone, gut, and lung development [27].
  • Mouse Rab23 regulates hedgehog signaling from smoothened to Gli proteins [28].

Other interactions of Gli1

  • The Sonic Hedgehog-Gli pathway regulates dorsal brain growth and tumorigenesis [29].
  • A similar regulatory mechanism involving the N-terminal region was also found for Gli3, but not for Gli1 [30].
  • We found that while neither Gli1 nor Gli3 are required for normal prostate ductal budding, the urogenital sinus (UGS) of the Gli2(-/-) mutant mouse displays aberrant ductal budding in utero [31].
  • In wild-type E11.0 molar tooth mesenchyme SHH-soaked beads induced the expression of Ptc and Gli1 [32].
  • We show here that the expression of Ptc, but not Gli1, was downregulated in the dental mesenchyme of Msx1 mutants [32].

Analytical, diagnostic and therapeutic context of Gli1


  1. Gli1 is important for medulloblastoma formation in Ptc1+/- mice. Kimura, H., Stephen, D., Joyner, A., Curran, T. Oncogene (2005) [Pubmed]
  2. Restriction of sonic hedgehog signalling during early tooth development. Cobourne, M.T., Miletich, I., Sharpe, P.T. Development (2004) [Pubmed]
  3. Suppressing Wnt Signaling by the Hedgehog Pathway through sFRP-1. He, J., Sheng, T., Stelter, A.A., Li, C., Zhang, X., Sinha, M., Luxon, B.A., Xie, J. J. Biol. Chem. (2006) [Pubmed]
  4. Dissecting the oncogenic potential of Gli2: deletion of an NH(2)-terminal fragment alters skin tumor phenotype. Sheng, H., Goich, S., Wang, A., Grachtchouk, M., Lowe, L., Mo, R., Lin, K., de Sauvage, F.J., Sasaki, H., Hui, C.C., Dlugosz, A.A. Cancer Res. (2002) [Pubmed]
  5. The SmoA1 mouse model reveals that notch signaling is critical for the growth and survival of sonic hedgehog-induced medulloblastomas. Hallahan, A.R., Pritchard, J.I., Hansen, S., Benson, M., Stoeck, J., Hatton, B.A., Russell, T.L., Ellenbogen, R.G., Bernstein, I.D., Beachy, P.A., Olson, J.M. Cancer Res. (2004) [Pubmed]
  6. Activation of the transcription factor Gli1 and the Sonic hedgehog signalling pathway in skin tumours. Dahmane, N., Lee, J., Robins, P., Heller, P., Ruiz i Altaba, A. Nature (1997) [Pubmed]
  7. Altered neural cell fates and medulloblastoma in mouse patched mutants. Goodrich, L.V., Milenković, L., Higgins, K.M., Scott, M.P. Science (1997) [Pubmed]
  8. Mediation of Sonic hedgehog-induced expression of COUP-TFII by a protein phosphatase. Krishnan, V., Pereira, F.A., Qiu, Y., Chen, C.H., Beachy, P.A., Tsai, S.Y., Tsai, M.J. Science (1997) [Pubmed]
  9. Dual degradation signals control Gli protein stability and tumor formation. Huntzicker, E.G., Estay, I.S., Zhen, H., Lokteva, L.A., Jackson, P.K., Oro, A.E. Genes Dev. (2006) [Pubmed]
  10. MIM/BEG4, a Sonic hedgehog-responsive gene that potentiates Gli-dependent transcription. Callahan, C.A., Ofstad, T., Horng, L., Wang, J.K., Zhen, H.H., Coulombe, P.A., Oro, A.E. Genes Dev. (2004) [Pubmed]
  11. Dysregulation of hedgehog signalling predisposes to synovial chondromatosis. Hopyan, S., Nadesan, P., Yu, C., Wunder, J., Alman, B.A. J. Pathol. (2005) [Pubmed]
  12. Several PATCHED1 missense mutations display activity in patched1-deficient fibroblasts. Bailey, E.C., Milenkovic, L., Scott, M.P., Collawn, J.F., Johnson, R.L. J. Biol. Chem. (2002) [Pubmed]
  13. Unique and complimentary activities of the Gli transcription factors in Hedgehog signaling. Lipinski, R.J., Gipp, J.J., Zhang, J., Doles, J.D., Bushman, W. Exp. Cell Res. (2006) [Pubmed]
  14. Sonic hedgehog pathway inhibition alters epididymal function as assessed by the development of sperm motility. Turner, T.T., Bang, H.J., Attipoe, S.A., Johnston, D.S., Tomsig, J.L. J. Androl. (2006) [Pubmed]
  15. Mouse intraflagellar transport proteins regulate both the activator and repressor functions of Gli transcription factors. Liu, A., Wang, B., Niswander, L.A. Development (2005) [Pubmed]
  16. The Shh signalling pathway in tooth development: defects in Gli2 and Gli3 mutants. Hardcastle, Z., Mo, R., Hui, C.C., Sharpe, P.T. Development (1998) [Pubmed]
  17. Gli1 can rescue the in vivo function of Gli2. Bai, C.B., Joyner, A.L. Development (2001) [Pubmed]
  18. Gli1 is a target of Sonic hedgehog that induces ventral neural tube development. Lee, J., Platt, K.A., Censullo, P., Ruiz i Altaba, A. Development (1997) [Pubmed]
  19. Mouse suppressor of fused is a negative regulator of sonic hedgehog signaling and alters the subcellular distribution of Gli1. Ding, Q., Fukami, S., Meng, X., Nishizaki, Y., Zhang, X., Sasaki, H., Dlugosz, A., Nakafuku, M., Hui, C. Curr. Biol. (1999) [Pubmed]
  20. Sonic hedgehog induces capillary morphogenesis by endothelial cells through phosphoinositide 3-kinase. Kanda, S., Mochizuki, Y., Suematsu, T., Miyata, Y., Nomata, K., Kanetake, H. J. Biol. Chem. (2003) [Pubmed]
  21. Adriamycin disruption of the Shh-Gli pathway is associated with abnormalities of foregut development. Arsic, D., Cameron, V., Ellmers, L., Quan, Q.B., Keenan, J., Beasley, S. J. Pediatr. Surg. (2004) [Pubmed]
  22. Sonic hedgehog signaling by the patched-smoothened receptor complex. Murone, M., Rosenthal, A., de Sauvage, F.J. Curr. Biol. (1999) [Pubmed]
  23. Myf5 is a direct target of long-range Shh signaling and Gli regulation for muscle specification. Gustafsson, M.K., Pan, H., Pinney, D.F., Liu, Y., Lewandowski, A., Epstein, D.J., Emerson, C.P. Genes Dev. (2002) [Pubmed]
  24. Overexpression of ptc1 inhibits induction of Shh target genes and prevents normal patterning in the neural tube. Goodrich, L.V., Jung, D., Higgins, K.M., Scott, M.P. Dev. Biol. (1999) [Pubmed]
  25. Expression profile of Gli family members and Shh in normal and mutant mouse limb development. Büscher, D., Rüther, U. Dev. Dyn. (1998) [Pubmed]
  26. Sonic hedgehog signaling regulates the expression of insulin-like growth factor binding protein-6 during fetal prostate development. Lipinski, R.J., Cook, C.H., Barnett, D.H., Gipp, J.J., Peterson, R.E., Bushman, W. Dev. Dyn. (2005) [Pubmed]
  27. Gli1 is not required for Pdgfralpha expression during mouse embryonic development. Zhang, X.Q., Afink, G.B., Hu, X.R., Forsberg-Nilsson, K., Nistér, M. Differentiation (2005) [Pubmed]
  28. Mouse Rab23 regulates hedgehog signaling from smoothened to Gli proteins. Eggenschwiler, J.T., Bulgakov, O.V., Qin, J., Li, T., Anderson, K.V. Dev. Biol. (2006) [Pubmed]
  29. The Sonic Hedgehog-Gli pathway regulates dorsal brain growth and tumorigenesis. Dahmane, N., Sánchez, P., Gitton, Y., Palma, V., Sun, T., Beyna, M., Weiner, H., Ruiz i Altaba, A. Development (2001) [Pubmed]
  30. Regulation of Gli2 and Gli3 activities by an amino-terminal repression domain: implication of Gli2 and Gli3 as primary mediators of Shh signaling. Sasaki, H., Nishizaki, Y., Hui, C., Nakafuku, M., Kondoh, H. Development (1999) [Pubmed]
  31. Functional compensation in Hedgehog signaling during mouse prostate development. Doles, J., Cook, C., Shi, X., Valosky, J., Lipinski, R., Bushman, W. Dev. Biol. (2006) [Pubmed]
  32. Msx1 is required for the induction of Patched by Sonic hedgehog in the mammalian tooth germ. Zhang, Y., Zhao, X., Hu, Y., St Amand, T., Zhang, M., Ramamurthy, R., Qiu, M., Chen, Y. Dev. Dyn. (1999) [Pubmed]
  33. Sonic hedgehog pathway genes are expressed and transcribed in the adult mouse epididymis. Turner, T.T., Bomgardner, D., Jacobs, J.P. J. Androl. (2004) [Pubmed]
  34. Complementary Gli activity mediates early patterning of the mouse visual system. Furimsky, M., Wallace, V.A. Dev. Dyn. (2006) [Pubmed]
  35. Zebrafish Gli3 functions as both an activator and a repressor in Hedgehog signaling. Tyurina, O.V., Guner, B., Popova, E., Feng, J., Schier, A.F., Kohtz, J.D., Karlstrom, R.O. Dev. Biol. (2005) [Pubmed]
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