ライフサイエンスコーパス: GLI3

1 H activation by suppressing the induction of GLI3.

2 ary cilia and elevated levels of full-length Gli3.

3 rom a poised to an active chromatin state at GLI3.

4 mpletely, despite considerable homology with Gli3.

5 ains by the opposing activities of Hand2 and Gli3.

6 aling triggers the dissociation of Sufu from Gli3.

7 on of either repressor or activator forms of Gli3.

8 vement of the binding site around its ligand GLI3.

9 ich can be rescued by reducing the dosage of Gli3.

10 ndance of the transcription factors GLI1 and GLI3.

11 ivating transcriptional regulators, GLI2 and GLI3.

12 t in primary cilia where it colocalizes with Gli3.

13 s enhanced ligase recruitment and stimulates Gli3(1-90) ubiquitination in in vitro ubiquitination ass

14 the Hedgehog transcriptional regulator Gli3 (Gli3(1-90)) to determine the role of weak motifs encoded

15 We map three such motifs in Gli3(1-90), the weakest of which has a millimolar dissoc

16 dgehog pathway-driven cancers and uncover in Gli3 a therapeutic target to treat these malignancies.

17 GLI3 transcriptional activators (GLI2(A) and GLI3(A)) and repressors (GLI2(R) and GLI3(R)) carry out

18 Mutations in GLI3, a component of the Sonic Hedgehog (Shh) signaling

19 GLI3, a mediator of hedgehog signaling, is a genetic cau

20 ion and directly suppresses the induction of GLI3, a negative regulator of SHH signaling.

21 Analysis of the mechanisms identified GLI3, a transcription factor regulated by the Hedgehog p

22 localization and transcriptional activity of GLI3, a transcriptional effector molecule of SHH, in can

23 First, DZIP1 interacts with GLI3, a transcriptional regulator for Hedgehog signaling

24 ffects of Nestin were mediated by binding to Gli3, a zinc finger transcription factor that negatively

25 ve GLI3(R) in the absence of normal Gli2 and Gli3 abrogates neurogenesis.

26 ng were disrupted in talpid(2) mutants, only GLI3 activator levels were significantly altered in the

27 ivity and normalizes aberrant Gli3 repressor/Gli3 activator ratios observed in Gli3+/- embryos.

28 This may contribute to the increased Gli3 activator/repressor ratios found in IFT mutants.

29 distribution, timing, and dosage of GLI2 and GLI3 activators and repressors.

30 tein trafficking, and the regulation of Gli2/Gli3 activators and repressors.

31 onnecting the MID1-PP2A protein complex with GLI3 activity control.

32 In this study, we show that Gli3 activity in the FL stroma is required for B cell de

33 Here, we show that Gli3 acts as a repressor in the developing murine calvar

34 ed by loss of Gli3, we conditionally deleted Gli3 after patterning was complete in mouse.

35 , and four subjects had somatic mutations in GLI3, an Shh pathway gene associated with HH.

36 a reduction in the expression of Irx3, Irx5, Gli3 and Alx4, all of which are upregulated in Hand2 lim

37 phosphorylation in the binding induction of GLI3 and betaTrCP1 may be a hallmark to authenticate GLI

38 pressor function of Brg was mediated through Gli3 and both the repressor and activator functions of B

39 d the mammalian kinesin Kif7 can also direct Gli3 and Ci processing in fly, underscoring a fundamenta

40 We found that both GLI3 and GLI1 bind to the pluripotency factor NANOG.

41 GLI3 and GLI2 are the transcriptional mediators generall

42 ngly, motif analysis at sites co-occupied by Gli3 and Hand2 uncovered mandibular-specific, low-affini

43 tionship, but genomic analysis revealed that Gli3 and Hand2 were enriched at regulatory elements for

44 ntagonistic actions of transcription factors Gli3 and Hand2.

45 ur work uncovers a mutual antagonism between Gli3 and Hox13 paralogs that has important implications

46 p suppresses activation of HSCs by targeting Gli3 and its expression is regulated by Smo-dependent NF

47 Early Wnt expression in the ZLI regulates Gli3 and L-fng to generate a permissive territory in whi

48 confirmed the expression of Zic1, Gli1, and Gli3 and other related key signaling mediators in osteob

49 ating a dose-dependent pattern regulation in Gli3 and Pbx1 compound mutations, we show that the globa

50 stellate cells (HSCs), reduces expression of Gli3 and profibrotic genes but induces gfap, the inactiv

51 uced SUFU stability and its capacity to bind GLI3 and promote its cleavage into the repressor form GL

52 imb digit number via its modifying effect on Gli3 and Shh expression levels.

53 We show that the interaction between Gli3 and Suppressor of Fused (Sufu) regulates the format

54 the nascent limb bud mesenchyme by impacting Gli3 and Tbx3 expression.

55 methylated, including TERT and the oncogenes GLI3 and TP73.

56 atory genes such as CTNNB1, TGBR2, JUN, FOS, GLI3, and MAPK3 involved in the WNT, TGF-beta, JNK, Hedg

57 an increase in Wnt8a and decreases in Gli2, Gli3, and Shh RNA levels.

58 alon depends on interactions between Shh and Gli3, and, moreover, demonstrate that both Shh and Gli3

59 escue of the polydactylous phenotype seen in Gli3+/- animals.

60 n mouse, here we show that functional 5'Hoxd-Gli3 antagonism acts indirectly, through Bmp signalling

61 isms that stabilize and destabilize Gli2 and Gli3 are essential for the proteins to promptly respond

62 cordingly, inactivating variants in GLI2 and GLI3 are found in several developmental disorders.

63 n to mouse mutants to establish that SHH and Gli3 are indeed necessary for mammalian mouth developmen

64 ing of Fgf/Wnt expression; thus both Shh and Gli3 are independently required to suppress it.

65 We propose that 5'Hoxd genes and Gli3 are part of an interdigital signalling centre that

66 Gli2 and Gli3 are primary transcriptional regulators that mediate

67 ysis and genetic mouse models, we identified Gli3 as a global regulator of superstructure patterning,

68 ing of skeletal muscle repair and identifies Gli3 as a potential target for regenerative medicine.

69 of IFT122 leads to accumulation of Gli2 and Gli3 at cilia tips while blocking the ciliary localizati

70 of the dorsal markers and Wnt targets, Pax6, Gli3, Axin2.

71 We also found that SLTM enhances GLI3 binding to chromatin and increases GLI3 repressor (

72 on assays show that the transcription factor GLI3 binds to the DR4 promoter and Hh requires an intact

73 immunoprecipitation assays demonstrated that GLI3 binds to the VMP1 promoter and complexes with the h

74 Nestin binding to Gli3 blocked Gli3 phosphorylation and its subsequent pro

75 does not lead to accumulation of full-length Gli3, but instead renders it labile, leading to its prot

76 nterfering RNA (siRNA)-targeted knockdown of GLI3, but not GLI1 or GLI2, restores DR4 expression and

77 both the full-length and repressor forms of Gli3, but not Gli2, were up-regulated in Spop mutants, a

78 s Hedgehog [Hh] pathway transcription factor Gli3) by immunofluorescence microscopy; and cilia functi

79 ve chromatin environment and functioned as a GLI3 co-repressor.

80 Furthermore, reduction of GLI2, but not GLI3, decreased the expression of both SOX9 and OPN, whe

81 ing conditional knockout mice, we found that Gli3 deficiency in endothelial cells did not affect isch

82 ischemic muscle repair, whereas in myocytes, Gli3 deficiency resulted in severely delayed ischemia-in

83 ription is increased in B-lineage cells from Gli3-deficient FL and showed that these cells expressed

84 Pax5 was reduced in developing B cells from Gli3-deficient FL but increased in Shh-deficient FL, and

85 In the Gli3-deficient FL, B cell development was reduced at mul

86 ion was increased in developing B cells from Gli3-deficient FLs.

87 in aberrant osteoblastic differentiation in Gli3-deficient mouse (Gli3(Xt-J/Xt-J)) and resulted in c

88 gs, forced Spop expression promotes Gli2 and Gli3 degradation and Gli3 processing.

89 ric nervous system was studied in Sufu(f/f), Gli3(Delta699), Wnt1-Cre, and Sox10(NGFP) mice using imm

90 ts the mitogenic sonic hedgehog pathway in a Gli3-dependent manner while enhancing retinoic acid sign

91 In a GLI3-dependent manner, SLTM promoted the formation of a

92 ield and preaxial polydactyly in a Gli1- and Gli3-dependent manner.

93 er, these findings suggest that dysregulated GLI3-dependent SHH signaling contributes to phenotypes o

94 ly, disrupt a Mediator-imposed constraint on GLI3-dependent Sonic Hedgehog (SHH) signaling.

95 during this early phase interferes with the Gli3-dependent specification of anterior progenitors, di

96 In fact, full-length Gli3 disappears with faster kinetics than the Gli3 repre

97 in glial cell production, removal of Gli2 or Gli3 does not alter adult SVZ neurogenesis.

98 Consistent with this finding, reducing Gli3 dosage greatly rescued the Spop mutant skeletal def

99 ulting Gli2(DeltaCLRKI) and Gli2(DeltaCLRKI);Gli3 double mutants resemble Gli2-null and Gli2;Gli3 dou

100 3 double mutants resemble Gli2-null and Gli2;Gli3 double mutants, respectively, suggesting the lack o

101 repressor/Gli3 activator ratios observed in Gli3+/- embryos.

102 downstream of HAND2 to refine the posterior Gli3 expression boundary.

103 quire differentiated status as they turn off Gli3 expression during neurogenesis.

104 Subsequently, Gli3 expression is not repressed posteriorly, Shh expres

105 ancer Genome Atlas AML data set reveals that GLI3 expression is silenced in most AML patient samples,

106 We demonstrate that Zic3 and Gli3 expression overlap in developing limbs and that Zic

107 By analyzing Gli3 extra-toe mutants (Gli3(Xt/Xt)), we found that Gli3

108 Mutant mice with no functional Gli3 (extra-toes, Gli3(Xt/Xt) mutants) display a massive

109 lso significantly impaired in HSA-Cre(ERT2); Gli3(Flox/Flox) mice, demonstrating that impaired myogen

110 ) ubiquitin ligase complex, targets Gli2 and Gli3 for degradation and negatively regulates Hedgehog (

111 GLI1, GLI2 and GLI3 form a family of transcription factors which regula

112 of Hedgehog pathway stimulation to create a Gli3 fragment that opposes the activity of the full-leng

113 evelopment, post-translational processing of Gli3 from activator to repressor antagonizes and posteri

114 gulator for Hedgehog signaling, and prevents GLI3 from entering the nucleus.

115 p in developing limbs and that Zic3 converts Gli3 from repressor to activator in vitro.

116 eins) results in destabilization of Gli2 and Gli3 full-length activators but not of their C-terminall

117 ucing Sufu into the MEFs stabilizes Gli2 and Gli3 full-length proteins and rescues Gli3 processing.

118 ts (MEFs) can restore the levels of Gli2 and Gli3 full-length proteins, but not those of their repres

119 FL showed increased B cell development, and Gli3 functioned to repress Shh transcription.

120 that has important implications for Hox and Gli3 gene regulation in the context of development and e

121 erved for SNPs in the EDAR, DCHS2, RUNX2 and GLI3 genes, respectively.

122 ncoding the zinc finger transcription factor GLI3 (GLI-Kruppel family member 3) have been identified

123 In contrast to Gli2 and Gli3, Gli1 is sparse in HSCs and is not increased upon a

124 on of the Hedgehog transcriptional regulator Gli3 (Gli3(1-90)) to determine the role of weak motifs e

125 fering with early prepatterning functions of Gli3/Gli3R or specification of anterior progenitors.

126 Gli3 has multiple weak SPOP binding motifs.

127 (SAG) increased levels of Ptch1, Gli1, Gli2, Gli3, Hes1 and Hes5, and stimulated the formation of pro

128 xpression of miR-378a-3p, directly targeting Gli3 in activated hepatic stellate cells (HSCs), reduces

129 Although the role of Gli3 in embryonic patterning has been extensively studie

130 The role of Gli3 in myocytes was then further investigated.

131 oligodendrocyte cell fates via repression of Gli3 in progenitors.

132 These findings suggest a novel role for Gli3 in regulating calvarial suture development by contr

133 Loss of one functional copy of Gli3 in Shh nulls rescues ventricular collapse and subst

134 Significantly, removing Gli3 in Smo conditional mutants largely rescues neurogen

135 e proteasome partially degrades or processes Gli3 in the absence of Hedgehog pathway stimulation to c

136 he role of the hedgehog transcription factor Gli3 in the cross-talk between angiogenesis and myogenes

137 In the absence of signaling, Sufu restrains Gli3 in the cytoplasm, promoting its processing into a r

138 th Dnchc2 and Wdr34 act between Smo and Gli2/Gli3 in the Hh pathway.

139 By conditionally removing Gli3 in the limb at multiple different time points, we u

140 the neural tube, revealing a crucial role of Gli3 in the maintenance of neural patterning.

141 Importantly, the accumulation of GLI3 in the nucleus is independent of loss of primary ci

142 bx3, and shifted and delayed upregulation of Gli3 in the prospective limb bud field.

143 inversely correlated with the expression of Gli3 in tumour and non-tumour tissues in human hepatocel

144 Knockdown of p300 impaired KRAS- and GLI3-induced activation of this promoter.

145 We propose that the Sufu-Gli3 interaction is a major control point in the Hedgeho

146 nt of all seven WD40 repeats of betaTrCP1 in GLI3 interaction.

147 Reintroduction of the repressor form of Gli3 into the Ftm (-/-) background restored optic cup fo

148 Our data suggest that GLI3 is a candidate gene contributing to KS etiology.

149 Since GLI3 is a more effective repressor, our results explain

150 These observations suggest that Gli3 is critical for OEC development in the nasal mucosa

151 The zinc finger transcription factor Gli3 is essential for normal development of the forebrai

152 Loss-of-function of the transcription factor Gli3 is known to disrupt olfactory development, however,

153 NIFICANCE STATEMENT The transcription factor Gli3 is necessary for correct development of the olfacto

154 ed in dual Ihh;Gli3 mutants, suggesting that Gli3 is normally a negative regulator of symphyseal deve

155 Our data reveal that Gli3 is required at the neural plate stage to regulate W

156 Moreover, Gli3 is required for maintaining the cortical progenitor

157 effective repressor, our results explain why GLI3 is required only for anterior limb patterning and w

158 demonstrate that RA-mediated suppression of GLI3 is sufficient to generate MNs in an SHH-independent

159 In addition, we found that Gli3 is upregulated in proliferating myoblasts by the ce

160 Combinations of putative etiologic variants (GLI3/KIF21A or EHMT2/UBE2I) in separate families were mo

161 Here, using a newly generated, tagged Gli3 knock-in mouse (Gli3(TAP) ), we performed proteomic

162 Furthermore, GLI3 knock-out hESCs can bypass the requirement for earl

163 assembly and shortly after the Hh effector, Gli3, leaves the cilium.

164 he absence of GLI3 or in the presence of low GLI3 levels, SLTM co-activated GLI activator (GLIA)-medi

165 knockdown and inhibition reduced full-length GLI3 levels.

166 al renal defects observed in humans with the GLI3-linked disease Pallister-Hall syndrome.

167 ilenced in most AML patient samples, and the GLI3 locus is abnormally methylated.

168 tra-toe mutants (Gli3(Xt/Xt)), we found that Gli3 loss-of-function compromises the onset of achaete-s

169 We found that Gli3 loss-of-function compromises the onset of Ascl-1(+)

170 whole-exome sequencing data, we identified a GLI3 loss-of-function variant in a KS individual.

171 We identified and validated a GLI3 loss-of-function variant in a KS individual.

172 st that Zic1, perhaps together with Gli1 and Gli3, may act as a link between mechanosensing and Wnt s

173 ple different time points, we uncovered four Gli3-mediated functions in limb development that occur a

174 In Gli3 mutant mice, Zic3 loss of function abrogates ectopi

175 ssociated the neurogenic defects observed in Gli3 mutants from lack of olfactory ensheathing cells in

176 nonoverlapping phenotypes between Ascl-1 and Gli3 mutants indicate that Ascl-1, while crucial for GnR

177 Further analysis of compound Shh;Gli3 mutants revealed an unexpected type of signaling ce

178 In Shh;Gli3 mutants, adjacent rings of Fgf8 and Wnt3a expressio

179 iferation was partially restored in dual Ihh;Gli3 mutants, suggesting that Gli3 is normally a negativ

180 lost in Shh null and expanded anteriorly in Gli3 mutants.

181 OECs development and demonstrate that human GLI3 mutations contribute to KS etiology.SIGNIFICANCE ST

182 Zic3 null;Gli3+/- neonates show rescue of the polydactylous phenot

183 asing the stability of the repressor form of GLI3, one of the transcription factors that ultimately r

184 Gli3, one of three vertebrate Gli transcription factors

185 In the absence of GLI3 or in the presence of low GLI3 levels, SLTM co-acti

186 binding to the N- and C-terminal regions of Gli3 or the C-terminal region of Gli2.

187 nd promoter activity of VMP1 upstream of the GLI3-p300 complex.

188 The effect of the Xs(J) mutation on the SHH/GLI3 pathway was analyzed by in situ hybridization analy

189 , we explored comparative binding pattern of GLI3 phosphopeptides against betaTrCP1.

190 Nestin binding to Gli3 blocked Gli3 phosphorylation and its subsequent proteolytic proc

191 GLI3 phosphorylation by Ser/Thr kinases is a primary fac

192 Conversely, GLI3 phosphorylation pattern at primary protein kinase A

193 However, if Gli3 plays a role in controlling GnRH-1 neuronal develop

194 o disrupt olfactory development, however, if Gli3 plays a role in GnRH-1 neuronal development is uncl

195 uled out, nor has it been determined whether Gli3 plays distinct roles in limb development at differe

196 mprehensive and thorough analysis demarcated GLI3 presence in the binding cleft shared by inter-blade

197 nd betaTrCP/Cul1 are required for endogenous Gli3 processing and that this is inhibited by Hh.

198 Our results indicated that GLI3 processing depends on the 19 phosphorylation sites

199 to increases in cellular cAMP levels and in Gli3 processing into its repressor form.

200 the cilium and the consequent suppression of Gli3 processing into its repressor form.

201 clear localization of Gli2, induces Gli2 and Gli3 processing into repressor forms, and activates cAMP

202 Gli3 processing is inhibited when any one component of t

203 GLI3 processing is triggered in an ubiquitin-dependent m

204 Although both GLI2 and GLI3 processing were disrupted in talpid(2) mutants, onl

205 n addition, anterior limb buds show aberrant Gli3 processing, consistent with perturbed SHH/GLI3 sign

206 i2 and Gli3 full-length proteins and rescues Gli3 processing.

207 ssion promotes Gli2 and Gli3 degradation and Gli3 processing.

208 betaTrCP1 may be a hallmark to authenticate GLI3 processing.

209 by direct binding of the RA receptor at the GLI3 promoter.

210 We found that Gli3 promotes myoblast differentiation through myogenic

211 Chromatin immunoprecipitation of DNA-Gli3 protein complexes from limb buds indicated that Gli

212 nal cord, likely through protecting Gli2 and Gli3 proteins from degradation.

213 recent findings that Sufu protects Gli2 and Gli3 proteins from proteasomal degradation.

214 nd, conversely, expression of a constitutive GLI3(R) in the absence of normal Gli2 and Gli3 abrogates

215 Thus unattenuated GLI3(R) is a primary inhibitor of adult SVZ NSC function

216 (A) and GLI3(A)) and repressors (GLI2(R) and GLI3(R)) carry out SHH signaling has not been addressed.

217 partial gliosis results from an increase in GLI3(R).

218 This study shows for the first time that Gli3-regulated postnatal myogenesis is necessary for mus

219 GLI3 regulates autophagy as well as the expression and p

220 In addition, we found that Gli3 regulates several proangiogenic factors, including

221 iquitination and proteasomal cleavage of the GLI3 regulator Fu.

222 tive modulation exerted by Hox13 paralogs on Gli3 regulatory sequences.

223 hat mediate the interaction between MID1 and GLI3 remained unknown.

224 o the DR4 promoter and Hh requires an intact GLI3-repression activity to silence DR4 expression.

225 inhibition by transient transfection of the Gli3 repressor (Gli3R) downregulated Gli1 and Gli2 expre

226 nces GLI3 binding to chromatin and increases GLI3 repressor (GLI3R) form protein levels.

227 n and colleagues show that tightly regulated GLI3 repressor activity is essential for Shh-dependent d

228 ties, we reveal an important contribution of Gli3 repressor activity to the Hh pathway activation and

229 digit 1 territory, correlates with increased Gli3 repressor activity, a Hoxd negative regulator, resu

230 n addition, using the Gli1 null allele and a Gli3 repressor allele, we reveal a specific genetic requ

231 l activity that incurs the formation of both GLI3 repressor and activator forms.

232 icant downregulation in the formation of the GLI3 repressor and increase in the ventral neuronal mark

233 further show that Spop directly targets the Gli3 repressor for ubiquitination and degradation.

234 naling by turning off PKA activity and hence Gli3 repressor formation.

235 and reveals the unexpected Sufu-independent Gli3 repressor function.

236 Hh pathway suppression by expression of the GLI3 repressor in GLI1+ myofibroblast progenitors limite

237 Constitutive expression of GLI3 repressor in Ptch1-deficient mice rescued ectopic P

238 ing genes that are normally inhibited by the Gli3 repressor is anteriorly expanded in mutant limbs.

239 We find that removal of the Gli3 repressor is dispensable for intestinal development

240 ts ciliary structure coinciding with reduced Gli3 repressor levels.

241 Finally, by altering the level of Gli3 repressor on a background of reduced Gli activator

242 Genetically restoring Gli3 repressor rescues the decreased indirect neurogenes

243 pathway; however, an increase in the protein Gli3 repressor reveals abnormal Hedgehog (Hh) signaling

244 li3 disappears with faster kinetics than the Gli3 repressor, the latter not requiring SPOP/Cul3 or be

245 polarizing activity and normalizes aberrant Gli3 repressor/Gli3 activator ratios observed in Gli3+/-

246 as seen with dysfunction of primary cilia or Gli3-repressor.

247 sults from the reduced formation of Gli2 and Gli3 repressors and early depletion of adenylyl cyclase

248 Ablation of Gli2 and Gli3 revealed a minor role for GLI2(R) and little requir

249 P53, ARID1A and CDH1) and new (MUC6, CTNNA2, GLI3, RNF43 and others) significantly mutated driver gen

250 Therefore, we generated Gli3;Runx2 compound mutant mice to study the effects of

251 i3 processing, consistent with perturbed SHH/GLI3 signaling.

252 he phenotype is associated with aberrant SHH/GLI3 signaling.

253 Neither Shh nor Gli3 single mutants show this forebrain double ring of F

254 remaining posterior limb patterning seen in Gli3 single mutants.

255 troporation experiments demonstrate that the Gli3, specifically Gli3R, is critical for specifying the

256 new insight into the regulation of Gli2 and Gli3 stability and processing by Sufu and Spop, and reve

257 nction of a Kif7/Sufu complex that regulates Gli3 stability and processing.

258 tein complexes from limb buds indicated that Gli3 strongly binds to the Has2 promoter region, suggest

259 and searched for mutation(s) in GLI1, GLI2, GLI3, SUFU, and SOX10.

260 n efficiency for its physiological substrate Gli3, suggesting that nuclear speckles are hotspots of u

261 and, moreover, demonstrate that both Shh and Gli3 suppress a potential Fgf/Wnt signaling source in th

262 newly generated, tagged Gli3 knock-in mouse (Gli3(TAP) ), we performed proteomic analyses and identif

263 document enhanced SHH pathway activation and GLI3-target gene induction coincident with impaired recr

264 paired recruitment of CDK8 onto promoters of GLI3-target genes, but not non-GLI3-target genes.

265 promoters of GLI3-target genes, but not non-GLI3-target genes.

266 Furthermore, by removing Gli2 in Gli3 temporal conditional knock-outs, we uncovered an es

267 We show that the species of Gli3 that accumulates at cilium tips is full-length and

268 rning and this correction over time required Gli3, the predominant repressor in neural patterning.

269 atterning did not occur when we also deleted Gli3, the primary GliR in the neural tube, revealing a c

270 tant for production of the repressor form of Gli3, the principal function of PKA in the Shh pathway i

271 ormation of the repressor and instead allows Gli3 to enter the nucleus, where it is converted into a

272 h signaling by determining the processing of Gli3 to its repressor form.

273 of the Hh pathway resulted in truncation of Gli3 to its repressor, Gli3R, and was shown to be necess

274 ds the hedgehog pathway transcription factor Gli3 to mediate the development of medulloblastomas of t

275 l tube and acts in combination with Gli2 and Gli3 to pattern ventral and intermediate neuronal cell t

276 DK8, identified herein to be a suppressor of GLI3 transactivation activity.

277 nitiate the formation of digit 1 by reducing Gli3 transcription and by enabling expansion of the 5'Ho

278 negative regulator, resulting from increased Gli3 transcription that, in turn, is due to the release

279 The specific mechanism by which the GLI2 and GLI3 transcriptional activators (GLI2(A) and GLI3(A)) an

280 than being driven by a Hh threshold, robust Gli3 transcriptional activity during skeletal and glossa

281 ptional activator GLI1 and a decrease in the GLI3 transcriptional repressor (GLI3R).

282 tivation and inhibiting the formation of the GLI3 transcriptional repressor.

283 Post-translational processing of GLI2 and GLI3 was aberrant in the developing facial prominences.

284 ass the patterning defects caused by loss of Gli3, we conditionally deleted Gli3 after patterning was

285 enous pathway transcription factors Gli2 and Gli3, we monitored their kinetics of accumulation in cil

286 ons are generated in the absence of Gli2 and Gli3, whereas astrocyte partial gliosis results from an

287 jority of slow-cycling NSCs express Gli2 and Gli3, whereas Gli1 is restricted ventrally and all three

288 ally, we show that GLI family zinc finger 3 (Gli3), which is an anterior repressor of tetrapod digits

289 and more potent inhibitors against activated GLI3 with a special emphasis on the anticancer activity.

290 the effects of decreasing Runx2 dosage in a Gli3(Xt-J/Xt-J) background.

291 of canonical Bmp signaling, was observed in Gli3(Xt-J/Xt-J) embryonic calvaria.

292 Gli3(Xt-J/Xt-J) Runx2(+/-) mice have neither craniosynos

293 tic differentiation in Gli3-deficient mouse (Gli3(Xt-J/Xt-J)) and resulted in craniosynostosis.

294 to the cortical hem are completely absent in Gli3(Xt/Xt) embryos, but some expression of those Wnts w

295 prisingly, GnRH-1 neurogenesis was intact in Gli3(Xt/Xt) mice but they displayed significant defects

296 ther the Wnt expression that persists in the Gli3(Xt/Xt) mutant neocortex activates Wnt/beta-catenin

297 nt mice with no functional Gli3 (extra-toes, Gli3(Xt/Xt) mutants) display a massive reduction in the

298 consistently decreased in the forebrains of Gli3(Xt/Xt) mutants, even prior to the formation of the

299 By analyzing Gli3 extra-toe mutants (Gli3(Xt/Xt)), we found that Gli3 loss-of-function compro

300 , an Shh inhibitor, or carrying mutations in Gli3(Xtj), an Shh-signaling effector, have morphogenetic