Gene Symbol: Gli3
Description: GLI-Kruppel family member GLI3
Alias: AI854843, AU023367, Bph, GLI3-190, GLI3FL, Pdn, add, transcriptional activator GLI3, GLI3 form of 190 kDa, GLI3 full length protein, anterior digit pattern deformity, brachyphalangy, extra toes, polydactyly Nagoya, zinc finger protein GLI3
Species: mouse
Products:     Gli3

Top Publications

  1. Masuya H, Sagai T, Wakana S, Moriwaki K, Shiroishi T. A duplicated zone of polarizing activity in polydactylous mouse mutants. Genes Dev. 1995;9:1645-53 pubmed
    ..Here we report that a new mouse mutant, Recombination induced mutant 4 (Rim4), and two old mutants, Hemimelic extra toes (Hx) and Extra toes (Xt), exhibit mirror-image duplications of the skeletal pattern of the digits...
  2. Perez Balaguer A, Puelles E, Wurst W, Martinez S. Shh dependent and independent maintenance of basal midbrain. Mech Dev. 2009;126:301-13 pubmed publisher
    ..Based on our results and recently published data, we suggest the existence of a specific genetic pathway for the specification of the mesencephalic red nucleus. Foxa2 could be the candidate gene that might control this genetic pathway. ..
  3. Takahashi M, Tamura K, Buscher D, Masuya H, Yonei Tamura S, Matsumoto K, et al. The role of Alx-4 in the establishment of anteroposterior polarity during vertebrate limb development. Development. 1998;125:4417-25 pubmed
    ..Analysis of polydactylous mutants indicate that the interaction between Alx-4 and Shh is independent of Gli3, a negative regulator of Shh in the limb...
  4. Liu A, Wang B, Niswander L. Mouse intraflagellar transport proteins regulate both the activator and repressor functions of Gli transcription factors. Development. 2005;132:3103-11 pubmed of multiple posteriorly restricted genes are expanded anteriorly in the mutant limbs, similar to loss of Gli3 transcriptional repressor function...
  5. Svärd J, Heby Henricson K, Henricson K, Persson Lek M, Rozell B, Lauth M, et al. Genetic elimination of Suppressor of fused reveals an essential repressor function in the mammalian Hedgehog signaling pathway. Dev Cell. 2006;10:187-97 pubmed
    ..Our data demonstrate that, in striking contrast to Drosophila, in mammals, Sufu has a central role, and its loss of function leads to potent ligand-independent activation of the Hh pathway. ..
  6. Ueta E, Kurome M, Teshima Y, Kodama M, Otsuka Y, Naruse I. Altered signaling pathway in the dysmorphogenesis of telencephalon in the Gli3 depressed mouse embryo, Pdn/Pdn. Congenit Anom (Kyoto). 2008;48:74-80 pubmed publisher
    The responsible gene of genetic polydactyly/arhinencephaly mouse (Pdn/Pdn) is Gli3. Pdn/Pdn exhibits absence of the olfactory bulb, suggesting telencephalic dysmorphogenesis...
  7. Chen Y, Knezevic V, Ervin V, Hutson R, Ward Y, Mackem S. Direct interaction with Hoxd proteins reverses Gli3-repressor function to promote digit formation downstream of Shh. Development. 2004;131:2339-47 pubmed
    ..Shh regulates digit formation largely by preventing cleavage of the Gli3 transcription factor to a repressor form that shuts off expression of Shh target genes...
  8. Szczepny A, Hime G, Loveland K. Expression of hedgehog signalling components in adult mouse testis. Dev Dyn. 2006;235:3063-70 pubmed
    ..Overall, the coordinated expression pattern of these genes in adult mouse testis indicates a role for Hh signalling in spermatogenesis. ..
  9. Haraguchi R, Motoyama J, Sasaki H, Satoh Y, Miyagawa S, Nakagata N, et al. Molecular analysis of coordinated bladder and urogenital organ formation by Hedgehog signaling. Development. 2007;134:525-33 pubmed
    ..Thus, the mesenchymal precursors for multiple urogenital structures derive from peri-cloacal mesenchyme and the coordination of urogenital organ formation from these precursors is orchestrated by Shh signals. ..

More Information

Publications101 found, 100 shown here

  1. Kang S, Graham J, Olney A, Biesecker L. GLI3 frameshift mutations cause autosomal dominant Pallister-Hall syndrome. Nat Genet. 1997;15:266-8 pubmed
    ..Am. J. Hum. Genet. 59, A81 (1996)), co-localizing the PHS locus and the GLI3 zinc finger transcription factor gene...
  2. Simon Chazottes D, Paces Fessy M, Lamour Isnard C, Guenet J, Blanchet Tournier M. Genomic organization, chromosomal assignment, and expression analysis of the mouse suppressor of fused gene (Sufu) coding a Gli protein partner. Mamm Genome. 2000;11:614-21 pubmed
    ..Sufu binds with all three Gli proteins, with different affinities. This report, in conjunction with recent studies, points out the importance of Sufu in mouse embryonic development. ..
  3. Lewis P, Dunn M, McMahon J, Logan M, Martin J, St Jacques B, et al. Cholesterol modification of sonic hedgehog is required for long-range signaling activity and effective modulation of signaling by Ptc1. Cell. 2001;105:599-612 pubmed
    ..Thus, cholesterol modification is essential for the normal range of signaling. It also appears to be necessary for appropriate modulation of signaling by the Shh receptor, Ptc1. ..
  4. Niederreither K, Vermot J, Schuhbaur B, Chambon P, Dolle P. Embryonic retinoic acid synthesis is required for forelimb growth and anteroposterior patterning in the mouse. Development. 2002;129:3563-74 pubmed
    ..We suggest that RA signaling cooperates with a posteriorly restricted factor such as dHand, to generate a functional zone of polarizing activity (ZPA). ..
  5. Lee M, Racine V, Jagadpramana P, Sun L, Yu W, Du T, et al. Ectodermal influx and cell hypertrophy provide early growth for all murine mammary rudiments, and are differentially regulated among them by Gli3. PLoS ONE. 2011;6:e26242 pubmed publisher
    ..Mice develop five pairs, numbered MR1 to MR5 from pectoral to inguinal position. We have previously shown that Gli3(Xt-J/Xt-J) mutant embryos, which lack the transcription factor Gli3, do not form MR3 and MR5...
  6. Lopez Rios J, Speziale D, Robay D, Scotti M, Osterwalder M, Nusspaumer G, et al. GLI3 constrains digit number by controlling both progenitor proliferation and BMP-dependent exit to chondrogenesis. Dev Cell. 2012;22:837-48 pubmed publisher
    Inactivation of Gli3, a key component of Hedgehog signaling in vertebrates, results in formation of additional digits (polydactyly) during limb bud development...
  7. Vortkamp A, Franz T, Gessler M, Grzeschik K. Deletion of GLI3 supports the homology of the human Greig cephalopolysyndactyly syndrome (GCPS) and the mouse mutant extra toes (Xt). Mamm Genome. 1992;3:461-3 pubmed
  8. Tole S, Ragsdale C, Grove E. Dorsoventral patterning of the telencephalon is disrupted in the mouse mutant extra-toes(J). Dev Biol. 2000;217:254-65 pubmed
    ..patterning in the extra-toes (J) (Xt(J)) mouse mutant, which carries a deletion in the Gli family member Gli3. We report that dorsoventral patterning of the telencephalon is dramatically disrupted in the Xt(J) mutant...
  9. Pan Y, Bai C, Joyner A, Wang B. Sonic hedgehog signaling regulates Gli2 transcriptional activity by suppressing its processing and degradation. Mol Cell Biol. 2006;26:3365-77 pubmed
    Gli2 and Gli3 are the primary transcription factors that mediate Sonic hedgehog (Shh) signals in the mouse. Gli3 mainly acts as a transcriptional repressor, because the majority of full-length Gli3 protein is proteolytically processed...
  10. Qu S, Niswender K, Ji Q, van der Meer R, Keeney D, Magnuson M, et al. Polydactyly and ectopic ZPA formation in Alx-4 mutant mice. Development. 1997;124:3999-4008 pubmed
    ..of other candidate regulators of anterior-posterior positional information in the limb bud, including HoxB8 and Gli3, is not altered in Alx-4 mutant embryos...
  11. May S, Ashique A, Karlen M, Wang B, Shen Y, Zarbalis K, et al. Loss of the retrograde motor for IFT disrupts localization of Smo to cilia and prevents the expression of both activator and repressor functions of Gli. Dev Biol. 2005;287:378-89 pubmed
    ..the phenotypic expression of both Gli activator and repressor function and for effective proteolytic processing of Gli3. Furthermore, we show that the localization of Smo to primary cilia is disrupted in mutants...
  12. Storm E, Kingsley D. GDF5 coordinates bone and joint formation during digit development. Dev Biol. 1999;209:11-27 pubmed
    ..Thus, GDF5 function in the digits demonstrates a link between cartilage development and joint development and is an important determinant of the pattern of bones and articulations in the digits. ..
  13. Milenkovic L, Goodrich L, Higgins K, Scott M. Mouse patched1 controls body size determination and limb patterning. Development. 1999;126:4431-40 pubmed
    ..The polydactyly was preceded by unexpected anterior limb bud transcription of Shh, so one function of ptc1 is to repress Shh expression in the anterior limb bud. ..
  14. Kim P, Mo R, Hui Cc C. Murine models of VACTERL syndrome: Role of sonic hedgehog signaling pathway. J Pediatr Surg. 2001;36:381-4 pubmed
    ..Mutant mice involving Shh signaling, the Shh transcription factors Gli2-/- and Gli3-/-, Gli2-/-;Gli3+/- double heterozygotes, and Shh-/- were analyzed...
  15. Mill P, Mo R, Hu M, Dagnino L, Rosenblum N, Hui C. Shh controls epithelial proliferation via independent pathways that converge on N-Myc. Dev Cell. 2005;9:293-303 pubmed
    ..These findings demonstrate that Shh signaling controls the rapid and patterned expansion of epithelial progenitors through convergent Gli-mediated regulation. ..
  16. Martinelli D, Fan C. Gas1 extends the range of Hedgehog action by facilitating its signaling. Genes Dev. 2007;21:1231-43 pubmed
    ..Our data support a model in which GAS1 helps transform the Hedgehog protein gradient into the observed activity gradient. We propose that Gas1 is an evolutionarily novel, vertebrate-specific Hedgehog pathway regulator. ..
  17. Endoh Yamagami S, Evangelista M, Wilson D, Wen X, Theunissen J, Phamluong K, et al. The mammalian Cos2 homolog Kif7 plays an essential role in modulating Hh signal transduction during development. Curr Biol. 2009;19:1320-6 pubmed publisher
    ..We also demonstrate a requirement for Kif7 in the efficient localization of Gli3 to cilia in response to Hh and for the processing of Gli3 to its repressor form...
  18. Johnson D. Extra-toes: anew mutant gene causing multiple abnormalities in the mouse. J Embryol Exp Morphol. 1967;17:543-81 pubmed
  19. Bulgakov O, Eggenschwiler J, Hong D, Anderson K, Li T. FKBP8 is a negative regulator of mouse sonic hedgehog signaling in neural tissues. Development. 2004;131:2149-59 pubmed
    ..Although it is expressed broadly, FKBP8 is required to antagonize SHH signaling primarily in neural tissues, suggesting that hedgehog signal transduction is subject to cell-type specific modulation during mammalian development. ..
  20. Lipinski R, Gipp J, Zhang J, Doles J, Bushman W. Unique and complimentary activities of the Gli transcription factors in Hedgehog signaling. Exp Cell Res. 2006;312:1925-38 pubmed
    ..Gli2 loss-of-function was associated with diminished Shh-induced target gene expression, while Gli3 loss-of-function was associated with increased basal and Shh-induced target gene expression...
  21. Wang C, Pan Y, Wang B. Suppressor of fused and Spop regulate the stability, processing and function of Gli2 and Gli3 full-length activators but not their repressors. Development. 2010;137:2001-9 pubmed publisher
    Gli2 and Gli3 are primary transcriptional regulators that mediate hedgehog (Hh) signaling...
  22. Rash B, Grove E. Shh and Gli3 regulate formation of the telencephalic-diencephalic junction and suppress an isthmus-like signaling source in the forebrain. Dev Biol. 2011;359:242-50 pubmed publisher
    ..Loss of one functional copy of Gli3 in Shh nulls rescues ventricular collapse and substantially restores the TDJ...
  23. Bai C, Stephen D, Joyner A. All mouse ventral spinal cord patterning by hedgehog is Gli dependent and involves an activator function of Gli3. Dev Cell. 2004;6:103-15 pubmed
    ..The full range of Gli activity and its dependence on Hh have not been determined, although the Gli2 activator and Gli3 repressor have been implicated...
  24. Butterfield N, Metzis V, McGlinn E, Bruce S, Wainwright B, Wicking C. Patched 1 is a crucial determinant of asymmetry and digit number in the vertebrate limb. Development. 2009;136:3515-24 pubmed publisher
    ..Hindlimbs display polydactyly (gain of digits) and a molecular profile similar to the Gli3 mutant extra-toes...
  25. Zeng H, Hoover A, Liu A. PCP effector gene Inturned is an important regulator of cilia formation and embryonic development in mammals. Dev Biol. 2010;339:418-28 pubmed publisher
    ..and Ptch1, two direct transcriptional targets of Hh signaling, is down-regulated, and the proteolytic processing of Gli3 is compromised...
  26. Ding Q, Motoyama J, Gasca S, Mo R, Sasaki H, Rossant J, et al. Diminished Sonic hedgehog signaling and lack of floor plate differentiation in Gli2 mutant mice. Development. 1998;125:2533-43 pubmed
    ..Our results imply that Gli2 is required to mediate high level but not low level Shh activity and show that the development of motor neurons can occur in the absence of floor plate induction. ..
  27. Litingtung Y, Chiang C. Specification of ventral neuron types is mediated by an antagonistic interaction between Shh and Gli3. Nat Neurosci. 2000;3:979-85 pubmed
    ..Here we show that Gli3 represses ventral fates in a dose-dependent manner...
  28. Kuijper S, Beverdam A, Kroon C, Brouwer A, Candille S, Barsh G, et al. Genetics of shoulder girdle formation: roles of Tbx15 and aristaless-like genes. Development. 2005;132:1601-10 pubmed
    ..We have studied the impact of Tbx15, Gli3, Alx4 and related genes on formation of the skeletal elements of the mouse shoulder and pelvic girdles...
  29. Tran P, Haycraft C, Besschetnova T, Turbe Doan A, Stottmann R, Herron B, et al. THM1 negatively modulates mouse sonic hedgehog signal transduction and affects retrograde intraflagellar transport in cilia. Nat Genet. 2008;40:403-410 pubmed publisher
    ..Specifically, the aln mutation uncouples the roles of anterograde and retrograde transport in SHH signaling, suggesting that anterograde IFT is required for GLI activation and that retrograde IFT modulates this event. ..
  30. Tuson M, He M, Anderson K. Protein kinase A acts at the basal body of the primary cilium to prevent Gli2 activation and ventralization of the mouse neural tube. Development. 2011;138:4921-30 pubmed publisher
    ..Genetic analysis shows that although PKA is important for production of the repressor form of Gli3, the principal function of PKA in the Shh pathway in neural development is to restrain activation of Gli2...
  31. Mo R, Freer A, Zinyk D, Crackower M, Michaud J, Heng H, et al. Specific and redundant functions of Gli2 and Gli3 zinc finger genes in skeletal patterning and development. Development. 1997;124:113-23 pubmed
    ..Interestingly, Gli2 and Gli3 (C.-c. Hui and A. L. Joyner (1993). Nature Genet...
  32. Persson M, Stamataki D, te Welscher P, Andersson E, Böse J, Ruther U, et al. Dorsal-ventral patterning of the spinal cord requires Gli3 transcriptional repressor activity. Genes Dev. 2002;16:2865-78 pubmed
    ..Here we identify a role for Gli3 transcriptional repressor activity in patterning the intermediate region of the spinal cord that complements the ..
  33. Wang B, Li Y. Evidence for the direct involvement of {beta}TrCP in Gli3 protein processing. Proc Natl Acad Sci U S A. 2006;103:33-8 pubmed
    ..Here we show that processing of the Gli3 protein, a homolog of Ci, also depends on phosphorylation of a set of four cAMP-dependent protein kinase sites that ..
  34. Blaess S, Corrales J, Joyner A. Sonic hedgehog regulates Gli activator and repressor functions with spatial and temporal precision in the mid/hindbrain region. Development. 2006;133:1799-809 pubmed
    ..development over time and space through positive regulation of the Gli activators (GliA) and inhibition of the Gli3 repressor (Gli3R)...
  35. Kise Y, Morinaka A, Teglund S, Miki H. Sufu recruits GSK3beta for efficient processing of Gli3. Biochem Biophys Res Commun. 2009;387:569-74 pubmed publisher
    ..Here, a novel role of mammalian Sufu is identified where it mediates the phosphorylation of Gli3 by GSK3beta, essential for Gli3 processing to generate a transcriptional repressor for Hh-target genes...
  36. Renault M, Roncalli J, Tongers J, Misener S, Thorne T, Jujo K, et al. The Hedgehog transcription factor Gli3 modulates angiogenesis. Circ Res. 2009;105:818-26 pubmed publisher
    ..To investigate the role of Gli3 in ischemic tissue repair...
  37. Ashe A, Butterfield N, Town L, Courtney A, Cooper A, Ferguson C, et al. Mutations in mouse Ift144 model the craniofacial, limb and rib defects in skeletal ciliopathies. Hum Mol Genet. 2012;21:1808-23 pubmed publisher
    ..This allelic series of mouse mutants provides a unique opportunity to uncover the underlying mechanistic basis of this intriguing subset of ciliopathies. ..
  38. Liem K, Ashe A, He M, Satir P, Moran J, Beier D, et al. The IFT-A complex regulates Shh signaling through cilia structure and membrane protein trafficking. J Cell Biol. 2012;197:789-800 pubmed publisher
  39. Grindley J, Bellusci S, Perkins D, Hogan B. Evidence for the involvement of the Gli gene family in embryonic mouse lung development. Dev Biol. 1997;188:337-48 pubmed
    Murine Gli, Gli2, and Gli3 are zinc finger genes related to Drosophila cubitus interuptus, a component of the hedgehog signal transduction pathway...
  40. Litingtung Y, Lei L, Westphal H, Chiang C. Sonic hedgehog is essential to foregut development. Nat Genet. 1998;20:58-61 pubmed
    ..These results indicate that Shh is required for the growth and differentiation of the oesophagus, trachea and lung, and suggest that mutations in SHH and its signalling components may be involved in foregut defects in humans. ..
  41. Ding Q, Fukami S, Meng X, Nishizaki Y, Zhang X, Sasaki H, et al. Mouse suppressor of fused is a negative regulator of sonic hedgehog signaling and alters the subcellular distribution of Gli1. Curr Biol. 1999;9:1119-22 pubmed
    ..Although the Gli1, Gli2, and Gli3 zinc finger proteins are known to be effectors of Hh signaling in vertebrates, the mechanisms regulating activity ..
  42. Barna M, Pandolfi P, Niswander L. Gli3 and Plzf cooperate in proximal limb patterning at early stages of limb development. Nature. 2005;436:277-81 pubmed
    ..Here we identify a genetic interaction between Gli3 (GLI-Kruppel family member 3) and Plzf (promyelocytic leukaemia zinc finger, also known as Zbtb16 and Zfp145), ..
  43. Yang L, Cai C, Lin L, Qyang Y, Chung C, Monteiro R, et al. Isl1Cre reveals a common Bmp pathway in heart and limb development. Development. 2006;133:1575-85 pubmed
    ..Tbx3 is required for heart and limb formation, and is mutated in ulnar-mammary syndrome. We provide evidence that the Tbx3 promoter is directly regulated by Bmp Smads in vivo. ..
  44. Han Y, Kim H, Dlugosz A, Ellison D, Gilbertson R, Alvarez Buylla A. Dual and opposing roles of primary cilia in medulloblastoma development. Nat Med. 2009;15:1062-5 pubmed publisher
    ..Primary cilia could serve as a diagnostic tool and provide new insights into the mechanism of tumorigenesis. ..
  45. Wen X, Lai C, Evangelista M, Hongo J, De Sauvage F, Scales S. Kinetics of hedgehog-dependent full-length Gli3 accumulation in primary cilia and subsequent degradation. Mol Cell Biol. 2010;30:1910-22 pubmed publisher
    ..By generating antibodies capable of detecting endogenous pathway transcription factors Gli2 and Gli3, we monitored their kinetics of accumulation in cilia upon Hh stimulation...
  46. Besse L, Neti M, Anselme I, Gerhardt C, Ruther U, Laclef C, et al. Primary cilia control telencephalic patterning and morphogenesis via Gli3 proteolytic processing. Development. 2011;138:2079-88 pubmed publisher the anterior telencephalon, the subpallium is expanded at the expense of the pallium, a phenotype reminiscent of Gli3 mutants. This phenotype indeed correlates with a decreased production of the short form of the Gli3 protein...
  47. Friedland Little J, Hoffmann A, Ocbina P, Peterson M, Bosman J, Chen Y, et al. A novel murine allele of Intraflagellar Transport Protein 172 causes a syndrome including VACTERL-like features with hydrocephalus. Hum Mol Genet. 2011;20:3725-37 pubmed publisher
    ..We propose a model in which mutation of Ift172 results in a specific class of abnormal cilia, causing disrupted Hh signaling while maintaining L-R axis determination, and resulting in the VACTERL-H phenotype. ..
  48. Liu J, Heydeck W, Zeng H, Liu A. Dual function of suppressor of fused in Hh pathway activation and mouse spinal cord patterning. Dev Biol. 2012;362:141-53 pubmed publisher
    ..cord D/V patterning remain controversial, particularly in light of recent findings that Sufu protects Gli2 and Gli3 proteins from proteasomal degradation...
  49. Balaskas N, Ribeiro A, Panovska J, Dessaud E, Sasai N, Page K, et al. Gene regulatory logic for reading the Sonic Hedgehog signaling gradient in the vertebrate neural tube. Cell. 2012;148:273-84 pubmed publisher
    ..Our findings reveal that morphogen interpretation is an emergent property of the architecture of a transcriptional network that provides robustness and reliability to tissue patterning. ..
  50. Johnson D. Brachyphalangy, an allele of extra-toes in the mouse. Genet Res. 1969;13:275-80 pubmed
  51. Schimmang T, Oda S, Ruther U. The mouse mutant Polydactyly Nagoya (Pdn) defines a novel allele of the zinc finger gene Gli3. Mamm Genome. 1994;5:384-6 pubmed
  52. Buscher D, Bosse B, Heymer J, Ruther U. Evidence for genetic control of Sonic hedgehog by Gli3 in mouse limb development. Mech Dev. 1997;62:175-82 pubmed
    ..In the polydactyly mouse mutant extra toes (Xt), possessing a null mutation of Gli3, Shh is additionally expressed in the anterior region of the limb bud...
  53. Matise M, Epstein D, Park H, Platt K, Joyner A. Gli2 is required for induction of floor plate and adjacent cells, but not most ventral neurons in the mouse central nervous system. Development. 1998;125:2759-70 pubmed
  54. Theil T, Alvarez Bolado G, Walter A, Ruther U. Gli3 is required for Emx gene expression during dorsal telencephalon development. Development. 1999;126:3561-71 pubmed
    ..Here, we report on forebrain development in the extra toes (Xt(J)) mouse mutant which carries a null mutation of the Gli3 gene...
  55. Kuijper S, Feitsma H, Sheth R, Korving J, Reijnen M, Meijlink F. Function and regulation of Alx4 in limb development: complex genetic interactions with Gli3 and Shh. Dev Biol. 2005;285:533-44 pubmed
    ..Total lack of reporter expression in a Gli3-/- background confirms the existence of Gli3-dependent and -independent Alx4 expression in the limb bud...
  56. Furimsky M, Wallace V. Complementary Gli activity mediates early patterning of the mouse visual system. Dev Dyn. 2006;235:594-605 pubmed
    ..This pathway is mediated by the Gli transcription factors (Gli1, Gli2, and Gli3) that differentially activate and repress the expression of specific downstream target genes...
  57. Wang C, Ruther U, Wang B. The Shh-independent activator function of the full-length Gli3 protein and its role in vertebrate limb digit patterning. Dev Biol. 2007;305:460-9 pubmed
    ..A/P) limb patterning in vertebrates is determined by the counteraction between the Sonic Hedgehog (Shh) and the Gli3 transcription factor...
  58. Kolpakova Hart E, Jinnin M, Hou B, Fukai N, Olsen B. Kinesin-2 controls development and patterning of the vertebrate skeleton by Hedgehog- and Gli3-dependent mechanisms. Dev Biol. 2007;309:273-84 pubmed
    ..We show that in Kif3a-deficient mesenchymal tissues both the repressor function of Gli3 transcription factor and the activation of the Shh transcriptional targets Ptch and Gli1 are compromised...
  59. Oh S, Huang X, Liu J, Litingtung Y, Chiang C. Shh and Gli3 activities are required for timely generation of motor neuron progenitors. Dev Biol. 2009;331:261-9 pubmed publisher
    ..Genetic studies of Shh(-/-);Gli3(-/-) double mutants indicated that the inhibition of Gli3 repressor activity by Shh is sufficient for the ..
  60. Ocbina P, Eggenschwiler J, Moskowitz I, Anderson K. Complex interactions between genes controlling trafficking in primary cilia. Nat Genet. 2011;43:547-53 pubmed publisher
  61. Hall J, Hooper J, Finger T. Expression of sonic hedgehog, patched, and Gli1 in developing taste papillae of the mouse. J Comp Neurol. 1999;406:143-55 pubmed
  62. te Welscher P, Fernandez Teran M, Ros M, Zeller R. Mutual genetic antagonism involving GLI3 and dHAND prepatterns the vertebrate limb bud mesenchyme prior to SHH signaling. Genes Dev. 2002;16:421-6 pubmed
    ..We show that the transcriptional repressor GLI3 restricts dHAND expression to posterior mesenchyme prior to activation of SHH signaling in mouse limb buds...
  63. Litingtung Y, Dahn R, Li Y, Fallon J, Chiang C. Shh and Gli3 are dispensable for limb skeleton formation but regulate digit number and identity. Nature. 2002;418:979-83 pubmed
    ..b>Gli3 (the gene implicated in human Greig cephalopolysyndactyly syndrome) is proposed to negatively regulate Shh by ..
  64. Hilton M, Tu X, Cook J, Hu H, Long F. Ihh controls cartilage development by antagonizing Gli3, but requires additional effectors to regulate osteoblast and vascular development. Development. 2005;132:4339-51 pubmed
    ..Here, we show that removal of Gli3 in Ihh-null mouse embryos restored normal proliferation and maturation of chondrocytes, but only partially rescued ..
  65. Liem K, He M, Ocbina P, Anderson K. Mouse Kif7/Costal2 is a cilia-associated protein that regulates Sonic hedgehog signaling. Proc Natl Acad Sci U S A. 2009;106:13377-82 pubmed publisher
    ..We conclude that Kif7 is a core regulator of Shh signaling that may also act as a ciliary motor. ..
  66. Zaki P, Collinson J, Toraiwa J, Simpson T, Price D, Quinn J. Penetrance of eye defects in mice heterozygous for mutation of Gli3 is enhanced by heterozygous mutation of Pax6. BMC Dev Biol. 2006;6:46 pubmed
    ..The Gli3 gene encodes a zinc finger transcription factor and homozygous loss-of-function mutations of Gli3 are lethal...
  67. Hill P, Götz K, Ruther U. A SHH-independent regulation of Gli3 is a significant determinant of anteroposterior patterning of the limb bud. Dev Biol. 2009;328:506-16 pubmed publisher
    ..Whereas GLI1 and GLI2 seem to be dispensable during limb development, GLI3 is especially crucial since all GLI3-associated human congenital diseases comprise limb malformations...
  68. Sagai T, Masuya H, Tamura M, Shimizu K, Yada Y, Wakana S, et al. Phylogenetic conservation of a limb-specific, cis-acting regulator of Sonic hedgehog ( Shh). Mamm Genome. 2004;15:23-34 pubmed
    ..Absence of the conserved sequence in limbless reptiles and amphibians and a cis- trans test using the Hx and Shh KO alleles suggest that the sequence is a cis-acting regulator that controls the polarized expression of Shh...
  69. McGlinn E, van Bueren K, Fiorenza S, Mo R, Poh A, Forrest A, et al. Pax9 and Jagged1 act downstream of Gli3 in vertebrate limb development. Mech Dev. 2005;122:1218-33 pubmed
    From early in limb development the transcription factor Gli3 acts to define boundaries of gene expression along the anterior-posterior (AP) axis, establishing asymmetric patterns required to provide positional information...
  70. Caspary T, Larkins C, Anderson K. The graded response to Sonic Hedgehog depends on cilia architecture. Dev Cell. 2007;12:767-78 pubmed
    ..Double mutant analysis indicates that Gli3 repressor activity is normal in hnn embryos, but Gli activators are constitutively active at low levels...
  71. Cheung H, Zhang X, Ribeiro A, Mo R, Makino S, Puviindran V, et al. The kinesin protein Kif7 is a critical regulator of Gli transcription factors in mammalian hedgehog signaling. Sci Signal. 2009;2:ra29 pubmed publisher
    ..Thus, Kif7 is a missing component of the mammalian Hh signaling machinery, implying a greater commonality between the Drosophila and mammalian system than the prevailing view suggests. ..
  72. Chen M, Wilson C, Li Y, Law K, Lu C, Gacayan R, et al. Cilium-independent regulation of Gli protein function by Sufu in Hedgehog signaling is evolutionarily conserved. Genes Dev. 2009;23:1910-28 pubmed publisher
    ..Taken together, these studies delineate important aspects of cilium-dependent and cilium-independent Hh signal transduction and provide significant mechanistic insight into Hh signaling in diverse species. ..
  73. Mukhopadhyay S, Wen X, Ratti N, Loktev A, Rangell L, Scales S, et al. The ciliary G-protein-coupled receptor Gpr161 negatively regulates the Sonic hedgehog pathway via cAMP signaling. Cell. 2013;152:210-23 pubmed publisher
    ..Constitutive Gpr161 activity increases cAMP levels and represses Shh signaling by determining the processing of Gli3 to its repressor form...
  74. Zhulyn O, Li D, Deimling S, Vakili N, Mo R, Puviindran V, et al. A switch from low to high Shh activity regulates establishment of limb progenitors and signaling centers. Dev Cell. 2014;29:241-9 pubmed publisher
    ..bud is prepatterned into anterior and posterior regions through the antagonistic actions of transcription factors Gli3 and Hand2...
  75. Sasaki H, Hui C, Nakafuku M, Kondoh H. A binding site for Gli proteins is essential for HNF-3beta floor plate enhancer activity in transgenics and can respond to Shh in vitro. Development. 1997;124:1313-22 pubmed
    ..Gli expression is restricted to the ventral part, while Gli2 and Gli3 are expressed throughout the neural tube and dorsally, respectively...
  76. Wang B, Fallon J, Beachy P. Hedgehog-regulated processing of Gli3 produces an anterior/posterior repressor gradient in the developing vertebrate limb. Cell. 2000;100:423-34 pubmed
    ..We demonstrate that PKA-dependent processing of vertebrate Gli3 in developing limb similarly generates a potent repressor in a manner antagonized by apparent long-range signaling ..
  77. Bai C, Joyner A. Gli1 can rescue the in vivo function of Gli2. Development. 2001;128:5161-72 pubmed
    ..In particular, Gli1 appears to be a constitutive activator, and Gli2 and Gli3 have repressor functions...
  78. Aoto K, Nishimura T, Eto K, Motoyama J. Mouse GLI3 regulates Fgf8 expression and apoptosis in the developing neural tube, face, and limb bud. Dev Biol. 2002;251:320-32 pubmed
    The zinc finger transcription factor GLI3 is considered a repressor of vertebrate Hedgehog (Hh) signaling...
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    ..Genetic studies of the effects of limiting accessibility of Shh within the limb support this model, in which the effect of the Shh morphogen is dictated by a temporal as well as a spatial gradient. ..
  80. Veltmaat J, Relaix F, Le L, Kratochwil K, Sala F, Van Veelen W, et al. Gli3-mediated somitic Fgf10 expression gradients are required for the induction and patterning of mammary epithelium along the embryonic axes. Development. 2006;133:2325-35 pubmed maturation of the surface ectoderm, and show that full expression of somitic Fgf10, co-regulated by GLI3, is required for the anteroposterior pattern in which the flank ectoderm acquires a mammary epithelial identity...
  81. Huang X, Goudy S, Ketova T, Litingtung Y, Chiang C. Gli3-deficient mice exhibit cleft palate associated with abnormal tongue development. Dev Dyn. 2008;237:3079-87 pubmed publisher
    ..We observed a high incidence of palate clefting in mice deficient in Gli3, known for its role as a repressor in the absence of Shh signaling...
  82. Joeng K, Long F. The Gli2 transcriptional activator is a crucial effector for Ihh signaling in osteoblast development and cartilage vascularization. Development. 2009;136:4177-85 pubmed publisher
    ..Previous work has shown that de-repression of the Gli3 repressor is the predominant mode through which Ihh controls chondrocyte proliferation and maturation, but that ..
  83. Lek M, Dias J, Marklund U, Uhde C, Kurdija S, Lei Q, et al. A homeodomain feedback circuit underlies step-function interpretation of a Shh morphogen gradient during ventral neural patterning. Development. 2010;137:4051-60 pubmed publisher
    ..These data establish that dynamic, non-graded changes in responding cells are essential for Shh morphogen interpretation, and provide a rationale to explain mechanistically the phenomenon of cellular memory of morphogen exposure. ..
  84. Miyagawa S, Matsumaru D, Murashima A, Omori A, Satoh Y, Haraguchi R, et al. The role of sonic hedgehog-Gli2 pathway in the masculinization of external genitalia. Endocrinology. 2011;152:2894-903 pubmed publisher
    ..The current study identified hedgehog signaling pathway as a key factor not only for initial development but also for sexually dimorphic development of the external genitalia in coordination with androgen signaling. ..
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    ..Recently, the human GLI3 gene has been proposed to be a candidate gene for GCPS...
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    ..The unique and shared functions of Gli3 and formin in these determinative events were genetically analyzed using single and double homozygous Extra-toes (..
  87. Dai P, Shinagawa T, Nomura T, Harada J, Kaul S, Wadhwa R, et al. Ski is involved in transcriptional regulation by the repressor and full-length forms of Gli3. Genes Dev. 2002;16:2843-8 pubmed
    Transcription factor Glioblastoma-3 (Gli3) is cleaved in the anterior region of the limb bud to generate its repressor form...
  88. Kuschel S, Ruther U, Theil T. A disrupted balance between Bmp/Wnt and Fgf signaling underlies the ventralization of the Gli3 mutant telencephalon. Dev Biol. 2003;260:484-95 pubmed
    ..we report on telencephalic development in Pdn mutant mice, which carry an integration of a retrotransposon in the Gli3 locus...
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    ..Accordingly, these mutant limbs may be reminiscent of an ancestral trunk extension, related to that proposed for arthropods. ..
  90. Capellini T, Di Giacomo G, Salsi V, Brendolan A, Ferretti E, Srivastava D, et al. Pbx1/Pbx2 requirement for distal limb patterning is mediated by the hierarchical control of Hox gene spatial distribution and Shh expression. Development. 2006;133:2263-73 pubmed
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    ..Here, we describe antagonistic interactions between posterior Hoxd genes and Gli3, suggesting that the latter product protects the AER from the deleterious effect of the formers, and we present ..
  92. Vierkotten J, Dildrop R, Peters T, Wang B, Ruther U. Ftm is a novel basal body protein of cilia involved in Shh signalling. Development. 2007;134:2569-77 pubmed
    ..The loss of Ftm affects the ratio of Gli3 activator to Gli3 repressor, suggesting an involvement of Ftm in Shh signalling...