ライフサイエンスコーパス: GLI3

1 mpletely, despite considerable homology with Gli3.

2 ains by the opposing activities of Hand2 and Gli3.

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

4 aling triggers the dissociation of Sufu from Gli3.

5 on of either repressor or activator forms of Gli3.

6 c and Shh, and reduced expression domains of Gli3.

7 ndance of the transcription factors GLI1 and GLI3.

8 ivating transcriptional regulators, GLI2 and GLI3.

9 vement of the binding site around its ligand GLI3.

10 t in primary cilia where it colocalizes with Gli3.

11 H activation by suppressing the induction of GLI3.

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

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

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

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

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

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

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

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

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

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

22 ing, which upregulates the truncated form of GLI3, a repressor of sonic hedgehog (SHH).

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

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

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

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

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

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

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

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

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

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

33 The requirement of Shh and Gli3 activities to promote the timely appearance of moto

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

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

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

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

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

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

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

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

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

43 GLI3 and GLI2 are the transcriptional mediators generall

44 ntagonistic actions of transcription factors Gli3 and Hand2.

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

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

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

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

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

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

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

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

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

54 through both downregulation of the truncated GLI3 and upregulation of full-length GLI3 expression.

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

56 appear to alter expression or processing of Gli3, and we demonstrate that transcriptional regulation

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

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

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

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

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

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

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

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

65 Gli2 and Gli3 are primary transcriptional regulators that mediate

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

67 TCH1 and GLI-Kruppel family members Gli1 and Gli3 as part of a potential molecular network associated

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

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

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

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

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

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

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

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

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

77 Gli3(-/-) cells segregate from Gli3(+/+) cells to form many abnormal structures particu

78 We found that Gli3(-/-) cells are present in all components of the Gli

79 are likely to be autonomous by studying how Gli3(-/-) cells develop when surrounded by a majority of

80 Gli3(-/-) cells in some locations are misspecified: in t

81 Gli3(-/-) cells segregate from Gli3(+/+) cells to form m

82 n cell autonomous defects and defects in the Gli3(-/-) cells that surround them.

83 resent in all components of the Gli3(-/-)<-->Gli3(+/+) chimeric forebrain, including dorsomedial stru

84 nsduction at the tip of cilia and preventing Gli3 cleavage into a repressor form in the presence of H

85 rovide direct genetic evidence that Gli2 and Gli3 collectively mediate all major aspects of Ihh funct

86 llectively, these observations indicate that Gli3 contributes to vessel growth under both ischemic an

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

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

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

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

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

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

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

94 Gli3-deficient mice also displayed reduced capillary den

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

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

97 l interfering RNA-mediated downregulation of Gli3 delayed tube formation (Matrigel), and Western anal

98 repressor expressed by a Gli3 mutant allele (Gli3(Delta699)) can mostly rescue the ventralized neural

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

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

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

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

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

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

105 dorso-ventral patterning function through a Gli3-derepression mechanism, Shh signaling is additional

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

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

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

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

110 3 double mutants resemble Gli2-null and Gli2;Gli3 double mutants, respectively, suggesting the lack o

111 Genetic studies of Shh(-/-);Gli3(-/-) double mutants indicated that the inhibition o

112 ddition of exogenous laminin-111 to Shh(-/-);Gli3(-/-) embryos restores the myotomal basement membran

113 In Gli3(-/-) embryos the dorsal telencephalon is abnormally

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

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

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

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

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

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

120 uncated GLI3 and upregulation of full-length GLI3 expression.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

138 METHODS AND Gli3-haploinsufficient (Gli3(+/-)) mice and their wild-t

139 Gli3 has multiple weak SPOP binding motifs.

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

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

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

143 ning and exhibits a genetic interaction with Gli3 in limb development.

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

145 oligodendrocyte cell fates via repression of Gli3 in progenitors.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

161 ventral patterning of the telencephalon when Gli3 is also removed.

162 regulated, and the proteolytic processing of Gli3 is compromised.

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

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

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

166 Moreover, Gli3 is required for maintaining the cortical progenitor

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

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

169 that an important cell autonomous action of Gli3 is to regulate the competence of dorsal telencephal

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

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

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

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

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

175 ) cells are present in all components of the Gli3(-/-)<-->Gli3(+/+) chimeric forebrain, including dor

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

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

178 ntricular ejection fractions were reduced in Gli3(+/-) mice compared to wild-type mice after surgical

179 METHODS AND Gli3-haploinsufficient (Gli3(+/-)) mice and their wild-type littermates were phy

180 portantly, the Gli3 repressor expressed by a Gli3 mutant allele (Gli3(Delta699)) can mostly rescue th

181 in cultivated mouse embryos and of Emx2 and Gli3 mutant embryos revealed that ectopic Fgf8 signallin

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

183 Accordingly, the Shh(-/-);Gli3(-/-) mutant spinal cord exhibits a delay in motor n

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

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

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

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

188 developing Gli3(-/-) telencephalic cells in Gli3(-/-) mutants result from a combination of their own

189 are initiated in normal numbers in Shh(-/-);Gli3(-/-) mutants, the subsequent appearance of motor ne

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

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

192 Gli3, one of three vertebrate Gli transcription factors

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

194 ver, promoter-reporter assays indicated that Gli3 overexpression does not modulate Gli-dependent tran

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

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

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

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

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

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

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

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

203 Gli3 processing is inhibited when any one component of t

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 cells, adenovirus-mediated overexpression of Gli3 promoted migration (modified Boyden chamber), small

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 tant for proper activator/repressor ratio of Gli3 protein in mice, both in the presence and absence o

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

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

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

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

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

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

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

220 nditions and provide the first evidence that Gli3 regulates angiogenesis and endothelial cell activit

221 GLI3 regulates autophagy as well as the expression and p

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

223 iquitination and proteasomal cleavage of the GLI3 regulator Fu.

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

225 tivator, either alone or in combination with Gli3 removal.

226 oordination of Wnt and SHH signaling through GLI3 represents a novel mechanism that regulates ventral

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

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

229 ble mutants indicated that the inhibition of Gli3 repressor activity by Shh is sufficient for the gen

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

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

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

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

234 of Sufu mutant embryos, indicating that the Gli3 repressor can function independently of Sufu.

235 More importantly, the Gli3 repressor expressed by a Gli3 mutant allele (Gli3(D

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

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

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

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

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

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

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

243 ous work has shown that de-repression of the Gli3 repressor is the predominant mode through which Ihh

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

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

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

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

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

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

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

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

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

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

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

255 remaining posterior limb patterning seen in Gli3 single mutants.

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

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

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

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

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

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

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

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 chanisms is that abnormalities of developing Gli3(-/-) telencephalic cells in Gli3(-/-) mutants resul

267 chimeras to identify some of the defects of Gli3(-/-) telencephalic cells that are likely to be auto

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

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

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

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

272 nt for Kif7 in the efficient localization of Gli3 to cilia in response to Hh and for the processing o

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

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

275 in response to Hh and for the processing of Gli3 to its repressor form.

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

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

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

279 of Ihh but requires simultaneous removal of Gli3 to restore osteoblast differentiation.

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

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

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

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

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

285 e induction of endothelial cell migration by Gli3 was dependent on Akt and ERK1/2 activation.

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

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

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

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

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

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

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

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

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

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

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

300 The Gli3 zinc finger transcription factor is expressed in de