ライフサイエンスコーパス: Ihh

1 Ihh deficiency caused condylar disorganization and growt

2 Ihh is normally downregulated in regions that will becom

3 Ihh regulates cartilage development through PTHrP-indepe

4 Ihh regulates ISC self-renewal and differentiation.

5 Ihh signaling mediates gastrin-induced proliferation of

6 Ihh-overexpressing transgenic animals were generated and

7 sing new experimental approaches that ablate Ihh specifically in Pgr-positive uterine cells of the mo

8 processes during post-natal life, we ablated Ihh in cartilage of neonatal mice and assessed the conse

9 Indian hedgehog (Ihh) signaling and abnormal Ihh protein distribution in the extracellular matrix.

10 stric epithelial proliferation by activating Ihh signaling in mice.

11 In addition, Ihh signaling can inhibit chondrocyte hypertrophy and sy

12 Although it is generally believed that all Ihh functions are mediated by the Gli family of transcri

13 Although Ihh(-/-) cells organize into chondrogenic condensations

14 ression in proliferating chondrocytes via an Ihh-independent pathway; phospho-CREB levels were compar

15 ebra periosteal cells in response to BMP and Ihh signaling, whereas distal CTs form from blastema cel

16 tic interaction between Wnt/beta-catenin and Ihh signaling in regulating synovial joint formation.

17 Both the Wnt/beta-catenin and Ihh signaling pathways play essential roles in crucial a

18 s of Atf4(-/-) bone marrow stromal cells and Ihh-blocking antibody eliminates this effect.

19 e P16/Ink4a, P21, GSK-3beta, Il-6, Ffg3, and Ihh were overexpressed.

20 ances in cross-talk between the BMP, FGF and Ihh/PTHrP pathways.

21 Thus, IGF and Ihh signaling appear to control the growth of the skelet

22 e, we report that disruption of both IGF and Ihh signaling resulted in additive reduction in the size

23 Remarkably, in both Ihh-/- and Ihh-/-; Gli3-/- embryos, vascularization promoted osteob

24 Gli2, were up-regulated in Spop mutants, and Ihh target genes Patched 1 (Ptch1) and parathyroid hormo

25 hanical activation of cell proliferation and Ihh gene expression.

26 However, the roles of PTHrP and Ihh in regulating earlier steps in chondrocyte different

27 is controlled at multiple steps by PTHrP and Ihh through the mutual regulation of their activities.

28 ties were accompanied by increased Runx2 and Ihh expression and increased Indian hedgehog signaling.

29 Interestingly, both Shh and Ihh are only expressed in the regenerating and developin

30 conditional approach to remove both Shh and Ihh functions from early mouse gut endoderm.

31 To examine the combined role of Shh and Ihh in intestinal morphogenesis, we generated transgenic

32 The expression of Shh and Ihh is quite unique since these genes have never been de

33 ial for long-range signaling by both Shh and Ihh ligands.

34 nto the distant past, revealing that Shh and Ihh must once have shared responsibilities in establishi

35 mo acts epistatic to Ptc1 to mediate Shh and Ihh signaling in the early mouse embryo.

36 that Disp1 function is essential for Shh and Ihh signaling in the mouse, and Disp1 gene dose regulate

37 n an ex vivo environment, both wild-type and Ihh mutant vessels invade the Ihh(-/-) cartilage, though

38 More importantly, we found that Wnt and Ihh signaling interact with each other in distinct ways

39 hondrocyte differentiation markers Col X and Ihh.

40 iated with endochondral ossification such as Ihh, Alpl, and Sdf-1.

41 me impairs Gli2-Foxc1 association as well as Ihh function.

42 that TGFbeta2 acts as a signal relay between Ihh and PTHrP in the regulation of cartilage hypertrophi

43 nstrates that Ihh is distributed well beyond Ihh expressing cells though the range of movement and si

44 Blocking Ihh function in primitive endoderm inhibits activation o

45 tero-posterior axis are orchestrated by both Ihh and Shh.

46 Remarkably, in both Ihh-/- and Ihh-/-; Gli3-/- embryos, vascularization prom

47 Indian hedgehog (encoded by Ihh) has been shown to be expressed in the uterine epith

48 upted in about 30% of columnar chondrocytes, Ihh action in the periarticular chondrocytes was upregul

49 livers, and some of these cells coexpressed Ihh, Ptc, and/or Gli2.

50 a shows, for the first time, that continuous Ihh action is required for completion of post-natal TMJ

51 Decreasing Ihh action in these mice reduced elongation of columns,

52 rst time, that postnatal chondrocyte-derived Ihh is essential for maintaining the growth plate and ar

53 Ovaries lacking Dhh/Ihh exhibit theca layer loss, blunted steroid production

54 Production of Dhh/Ihh in granulosa cells requires growth differentiation f

55 a growth-plate-like structure with distinct Ihh, collagen X, and osteopontin expression patterns.

56 Proliferation was partially restored in dual Ihh;Gli3 mutants, suggesting that Gli3 is normally a neg

57 Although ectopic Ihh does not induce overt ossification along the entire

58 gesting a synergistic effect between ectopic Ihh and endogenous factors such as the bone morphogeneti

59 lin D1 is markedly downregulated when either Ihh or Smo activity is removed from chondrocytes, indica

60 n of Atf4 in chondrocytes induces endogenous Ihh mRNA, and Atf4 directly binds to the Ihh promoter an

61 th factor-evoked ERK activation and enhanced Ihh and Pthrp expression, whereas fibroblast growth fact

62 Deletion of intestinal epithelial Ihh disrupted the intestinal mesenchymal architecture, d

63 Intestinal epithelial Ihh signals to the mesenchymal compartment to regulate f

64 genitor cell population to prevent excessive Ihh production.

65 Treatment with exogenous Ihh did not fully restore normal proteoglycan levels in

66 cells that accumulate in PBC livers express Ihh or Hh-target genes including the Hh-receptor, Patche

67 Scattered stromal cells also expressed Ihh.

68 phenotypes of embryo yolk sacs deficient for Ihh or SMO: Whereas Ihh(-/-) yolk sacs can form blood ve

69 amined the ability of ES cells deficient for Ihh or smoothened (Smo), which encodes a receptor compon

70 ly establish Gli3 as a critical effector for Ihh activity in the developing skeleton, but also identi

71 ng a transmembrane protein indispensable for Ihh signaling) has been only partially successful, due t

72 A role for Ihh in yolk sac function is suggested by the observation

73 hedgehog (Shh), a functional substitute for Ihh, stimulates expression of Tgfb2 and Tgfb3 mRNA in th

74 REB levels were comparable in cartilage from Ihh(-/-) and wild-type mice.

75 signed to segregate the activity of Shh from Ihh.

76 Furthermore, Ihh mediates the mechanotransduction process in a bone m

77 by increased expression of Indian Hedgehog (Ihh) and hyperproliferation of surface mucous cells.

78 nied by an up-regulation of Indian Hedgehog (Ihh) and maintenance of Hh pathway activity.

79 olume, and up-regulation of Indian hedgehog (Ihh) and of collagen type X--all indicative of chondrocy

80 signaling cascade involving Indian hedgehog (Ihh) and parathyroid hormone related peptide (PTHrP) has

81 thway activation, increased Indian hedgehog (Ihh) and parathyroid hormone-related protein (Pthrp, als

82 Indian hedgehog (Ihh) and PTHrP signaling play crucial roles in regulatin

83 s, sonic hedgehog (Shh) and indian hedgehog (Ihh) are secreted by the endoderm of the mammalian gut,

84 We identify Indian hedgehog (Ihh) as a novel downstream target of AR in external geni

85 Indian hedgehog (Ihh) controls multiple aspects of endochondral skeletal

86 Indian hedgehog (Ihh) controls multiple aspects of endochondral skeletal

87 Indian hedgehog (Ihh) critically regulates multiple aspects of endochondr

88 s Desert hedgehog (Dhh) and Indian hedgehog (Ihh) from granulosa cells.

89 We identified the Indian hedgehog (Ihh) gene as a target of BMP signaling.

90 in (Ocn) in osteoblasts and indian hedgehog (Ihh) in chondrocytes.

91 We examined the role of Indian hedgehog (Ihh) in mesenchymal organization and the mechanisms by w

92 to mechanical induction of Indian hedgehog (Ihh) in primary chicken chondrocytes cultured in 3-dimen

93 Indian hedgehog (Ihh) is essential for chondrocyte and osteoblast prolife

94 Indian hedgehog (Ihh) is essential for embryonic mandibular condylar grow

95 ous studies have shown that Indian hedgehog (Ihh) is expressed in the visceral endoderm both in the v

96 Indian hedgehog (Ihh) is expressed normally in the growth plates of Evc(-

97 Indian hedgehog (Ihh) is indispensable for development of the osteoblast

98 Indian hedgehog (Ihh) is indispensable for osteoblast differentiation dur

99 The expression of Indian hedgehog (Ihh) is markedly decreased, whereas the expression of ot

100 ly secreted Sonic (Shh) and Indian hedgehog (Ihh) proteins that directly signal to adjacent mesoderm.

101 tes that also expressed the Indian hedgehog (Ihh) receptor and transcriptional target Patched 1(Ptch1

102 Indian Hedgehog (Ihh) regulates chondrocyte and osteoblast differentiatio

103 Indian hedgehog (Ihh) regulates endochondral ossification in both a parat

104 Here we asked whether Indian hedgehog (Ihh) regulates symphyseal cartilage development and grow

105 Indian Hedgehog (Ihh) regulates tissue morphogenesis.

106 Loss of Indian hedgehog (Ihh) results in reduction in pancreas size, indicating a

107 th plates showed diminished Indian hedgehog (Ihh) signaling and abnormal Ihh protein distribution in

108 igated the role of Disp1 in Indian hedgehog (Ihh) signaling in the developing bone bypassing the leth

109 Indian hedgehog (Ihh) signaling is indispensable for osteoblast different

110 d that most likely reflects Indian hedgehog (Ihh) signaling originating from the underlying gut endod

111 ells 1 (Nfatc1), Runx3, and Indian hedgehog (Ihh) signaling pathways, although the mechanistic insigh

112 related peptide (PTHrP) and Indian hedgehog (Ihh) signaling tightly regulates chondrocyte proliferati

113 reduced Ihh expression and Indian hedgehog (Ihh) signaling.

114 ndral skeleton, a target of Indian hedgehog (Ihh) signaling.

115 on of either Sonic (Shh) or Indian Hedgehog (Ihh) under control of the human Pax4-promoter.

116 ondrogenic genes, including Indian hedgehog (Ihh), a critical mediator of mechanotransduction.

117 ts genetically with that by Indian hedgehog (Ihh), a locally produced growth signal for the endochond

118 Indian hedgehog (Ihh), a member of the hedgehog (Hh) family of proteins,

119 ly detectable expression of Indian hedgehog (Ihh), collagen X (Col10a1), Vegf (Vegfa), MMP-13 (Mmp13)

120 Indian hedgehog (Ihh), one of the three mammalian hedgehog (Hh) proteins,

121 Indian hedgehog (Ihh), patched (Ptc), and Gli3 are expressed at low level

122 otein (PTHrP), regulated by Indian hedgehog (Ihh), prevents premature hypertrophic differentiation, t

123 ), sonic hedgehog (Shh) and Indian hedgehog (Ihh), we demonstrate that Disp1 genetically interacts wi

124 Indian hedgehog (Ihh), which is predominantly expressed in prehypertrophi

125 omain typically occupied by Indian hedgehog (Ihh).

126 nied by early activation of Indian hedgehog (Ihh).

127 zones independently of the Indian hedgehog (Ihh)/parathyroid hormone-related peptide (PTHrP) negativ

128 In Ihh(-/-) embryos, skeletal muscle development appears ab

129 In Ihh-null mice, however, symphyseal development was defec

130 4(-/-) embryos and rectifies the decrease in Ihh expression, Hh signaling, proliferation and accelera

131 stly, we studied postnatal mice deficient in Ihh in cartilage; their cranial base defects only minima

132 e for the failure of osteoblast formation in Ihh-null embryos.

133 Here, we show that removal of Gli3 in Ihh-null mouse embryos restored normal proliferation and

134 Loss of muscle mass in Ihh null mouse embryos is accompanied by a dramatic incr

135 ses were accompanied by marked reductions in Ihh and PTHrP as well as sFRP-1, an endogenous Wnt signa

136 skeletal muscle mass similar to that seen in Ihh(-/-) mouse embryos.

137 ophy, we have both activated and inactivated Ihh signaling in the absence of PTHrP during endochondra

138 on of its epithelial target genes, including Ihh, in the Wnt7a-Cre(+)PR(f/-) mice.

139 hondrocyte differentiation markers including Ihh, Col X, and Runx2.

140 bitor treatment of chondroid cells increased Ihh and Pthrp expression.

141 Sonic (Shh) and Indian (Ihh) hedgehog are expressed in the epithelium throughout

142 reduction in the combined epithelial Indian (Ihh) and Sonic (Shh) hedgehog signal leads to mislocaliz

143 Sonic (Shh), Indian (Ihh), and Desert (Dhh) hedgehog constitute the repertoir

144 In this negative-feedback loop, Ihh inhibits hypertrophic differentiation by regulating

145 he role of Ihh in myogenesis, we manipulated Ihh expression in the developing chick hindlimb.

146 transcription activator critically mediates Ihh function in osteoblastogenesis.

147 been established which Gli protein mediates Ihh activity in skeletal development.

148 n important function for CSPGs in modulating Ihh signaling in the developing growth plate, and highli

149 Our results demonstrate that neither Shh nor Ihh is required for mammary gland morphogenesis and func

150 Atf4 in chondrocytes is required for normal Ihh expression and for its paracrine effect on osteoblas

151 ested by the observation that roughly 50% of Ihh(-/-) mice die at mid-gestation, potentially owing to

152 the hypertrophic cartilage in the absence of Ihh but requires simultaneous removal of Gli3 to restore

153 In the absence of Ihh, cells of the osteoblast lineage fail to activate th

154 red for normal transcriptional activation of Ihh target genes.

155 Atf4 as a novel transcriptional activator of Ihh in chondrocytes that paces longitudinal bone growth

156 at cholesterol, by modifying the activity of Ihh (another of the Hedgehog family proteins) in the gro

157 possibly by altering the normal activity of Ihh, results in suppressed longitudinal bone growth and

158 Direct analysis of Ihh trafficking in the target field demonstrates that Ih

159 i3 collectively mediate all major aspects of Ihh function during endochondral skeletal development.

160 els in mutant cultures, but a combination of Ihh and BMP-2 did.

161 italia and show that conditional deletion of Ihh inhibits penile masculinization.

162 atial-specific manner; postnatal deletion of Ihh resulted in loss of columnar structure, premature va

163 sed with mice with conditional disruption of Ihh in the small intestine epithelium.

164 outgrowth were due in part to disruption of Ihh signaling during endochondral bone formation.

165 intestinal epithelial-specific disruption of Ihh.

166 sed a model where TGFbeta acts downstream of Ihh and upstream of PTHrP in a cascade of signals that r

167 e that Wnt signaling functions downstream of Ihh in development of the osteoblast lineage.

168 Beta-catenin is required downstream of Ihh signaling and osterix expression for osteoblast diff

169 muscle mass appears to be a direct effect of Ihh since ectopic expression of Ihh by RCAS retroviral i

170 vious efforts to delineate direct effects of Ihh on chondrocytes by Col2-Cre-mediated ablation of Smo

171 Despite the pro-osteogenic effects of Ihh on periosteal cell differentiation, mechanical artic

172 s important role by dampening the effects of Ihh-PTHrP together with sFRP-1.

173 PC-Shh(KO)/GKO mice increased expression of Ihh and proliferation within the surface epithelium comp

174 MiR-365 increases expression of Ihh and the hypertrophic marker type X collagen, whereas

175 cal stress greatly induces the expression of Ihh by chondrocytes.

176 ct effect of Ihh since ectopic expression of Ihh by RCAS retroviral infection of chicken embryo hindl

177 In contrast, chronic over-expression of Ihh in the intestinal epithelium leads to progressive ex

178 Lastly, AY 9944 decreased the expression of Ihh in the metatarsal growth plate.

179 ssification is delayed and the expression of Ihh target genes inhibited.

180 Foxc1 stimulates expression of Ihh target genes, including PTHrP and Col10a1, through i

181 e epithelium was collected and expression of Ihh was quantified by laser capture microdissection foll

182 In this study, we show a novel function of Ihh.

183 Lower induction of Ihh, Ptc, and Hoxa10 is seen in response to progesterone

184 able to override the osteogenic influence of Ihh on the periosteum, but does not interfere with the c

185 rowth plates of these mice exhibit a lack of Ihh, PTHrP-R, and Col10 expression indicating a loss of

186 ts, the condyles displayed reduced levels of Ihh expression, H4C-positive proliferating chondroprogen

187 Direct measurements of Ihh binding to defined GAG chains demonstrated that Ihh

188 r no Ptch1-lacZ staining and no migration of Ihh expressing cells into the developing placenta.

189 ndent upregulation but also misexpression of Ihh, leading to abnormal phalanges, fusion of sutures an

190 The number of Ihh+ cells/portal triad was 6-fold greater in PBC livers

191 Overexpression of Ihh caused PTHrP upregulation, elongation of columns, an

192 1 is an important transcriptional partner of Ihh-Gli2 signalling during endochondral ossification, an

193 In conclusion, the skeletal phenotype of Ihh(-/-) embryos represents the sum of disturbances in t

194 er distance, reflecting the reduced range of Ihh movement.

195 Reduction of Ihh in chicken embryo hindlimbs reduced skeletal muscle

196 R binding sites in the 5'-flanking region of Ihh.

197 cyte hypertrophy, while a down-regulation of Ihh expression may be responsible for a significant redu

198 S-PGs to exert their roles via regulation of Ihh signaling topography and action.

199 , Spop is an important positive regulator of Ihh signaling and skeletal development.

200 To further examine the role of Ihh in myogenesis, we manipulated Ihh expression in the

201 required for the paracrine signaling role of Ihh in the skeleton.

202 Our results revealed a novel role of Ihh signaling in promoting chondrocyte hypertrophy indep

203 whether there is a PTHrP-independent role of Ihh signaling in regulating chondrocyte hypertrophy, we

204 We uncovered previously unexpected roles of Ihh signaling in synovial joint formation and the essent

205 Transcription of Ihh in ovariectomized mice is induced by progesterone bu

206 Transcription of Ihh increases dramatically in the luminal epithelium and

207 Transplants of Ihh-null anlagen also developed normally.

208 In these models, upregulation of Ihh action in the periarticular region was also observed

209 r in the growth plate caused upregulation of Ihh action, PTHrP upregulation, acceleration of periarti

210 rvival, beta-catenin is required upstream of Ihh signaling to inhibit chondrocyte apoptosis.

211 Analysis was conducted on Ihh to determine whether PR directly regulates epithelia

212 and that FGF exerts antagonistic effects on Ihh expression.

213 ies arise following removal of either Shh or Ihh.

214 og (Shh) protein in vitro, or overexpressing Ihh in the cartilage of PTHrP(-/-) embryos or inactivati

215 fects are observed in both Pax4-Shh and Pax4-Ihh transgenic lines, suggesting that regulation of the

216 ous Wnt signaling antagonist and a potential Ihh signaling target.

217 te that BMP signaling is required to promote Ihh expression, and to inhibit activation of STAT and ER

218 Cotransfection of the proximal Ihh promoter with PR demonstrated that PR directly regul

219 Consequently, a PTHrP-Ihh feedback loop is established, but over a shorter dis

220 titutive ERK1/2 activation, strongly reduced Ihh expression and decreased chondrocyte proliferation a

221 5(-/-) mice that are associated with reduced Ihh expression and Indian hedgehog (Ihh) signaling.

222 nding suggests that the hormone may regulate Ihh through both nuclear receptor-dependent and -indepen

223 h PR demonstrated that PR directly regulates Ihh transcription.

224 independent Notch signaling likely regulates Ihh responsiveness during cartilage and bone development

225 ey act, at least in part, by down-regulating Ihh signaling, Fgfr3, and Runx2 and by up-regulating Bmp

226 pregulate Cyclin D1 and to antagonize Runx2, Ihh, and collagen X expression when Zfp521 was absent.

227 In the ex vivo setting, Ihh(-/-) cells differentiate into osteoblasts and deposi

228 Here we show that Shh, Ihh, ptc-1, and ptc-2 are expressed during lens regenera

229 Smo and Shh/Ihh compound mutants have identical phenotypes: embryos

230 of the Hh pathway, such as Shh, Smo and Shh/Ihh compound mutants, also have laterality defects.

231 t arrest in cartilage differentiation, since Ihh(-/-) chondrocytes undergo hypertrophy and terminal d

232 ated by increased transcript levels of Sox9, Ihh, Col2a1, and Col10a1.

233 lineage requires sequential, stage-specific, Ihh and canonical Wnt/beta-catenin signaling to promote

234 These findings indicate that BMP stimulates Ihh expression.

235 Strong Ihh expression was detected in most bile ductular cells.

236 occur when Shh is not expressed, suggesting Ihh acts directly on fetal myoblasts to regulate seconda

237 In summary, Ihh is required for multiple processes during synchondro

238 ineage in the developing long bones and that Ihh functions in conjunction with other factors such as

239 These results demonstrate that Ihh acts on periarticular chondrocytes to stimulate thei

240 rine cells of the mouse, we demonstrate that Ihh is an essential mediator of Pgr action in the uterus

241 ken together, these results demonstrate that Ihh signaling is directly required for the osteoblast li

242 ding to defined GAG chains demonstrated that Ihh interacts with CS, particularly chondroitin-4-sulfat

243 icking in the target field demonstrates that Ihh is distributed well beyond Ihh expressing cells thou

244 nt study has not only provided evidence that Ihh signaling directly controls PTHrP expression and cho

245 Previous studies indicate that Ihh signaling in the long bones is essential for initial

246 s removed from chondrocytes, indicating that Ihh regulates chondrocyte proliferation at least in part

247 rter and genome-editing studies in mice that Ihh is regulated by a constellation of at least nine enh

248 erses transcription-PCR assays revealed that Ihh is up-regulated in embryonic cells upon BMP treatmen

249 We show that Ihh is a direct target of BMP pathways in chondrocytes,

250 Here we show that Ihh stimulates differentiation of periarticular to colum

251 -immunoprecipitation experiments showed that Ihh binds to the major cartilage CSPG aggrecan via its C

252 We suggest that Ihh acts in vivo on a potential progenitor cell to promo

253 Our data suggest that Ihh may transduce mechanical signals during cartilage gr

254 These data suggest that Ihh positively controls differentiation of periarticular

255 Our data suggest that Ihh promotes fetal myoblast survival during their differ

256 essive Patched-1 expression, suggesting that Ihh distribution was wider and responsible for such exce

257 is in the adjacent epiblast, suggesting that Ihh is an endogenous signal that plays a key role in the

258 The Ihh(-/-) cranial bases displayed reduced growth and chon

259 absence of blood vessels is not because the Ihh(-/-) skeleton is anti-angiogenic; in fact, in an ex

260 natal life, mesenchymal cells expressing the Ihh receptor Patched1 were present anterior to the Ihh-e

261 RT-PCR analysis in the Ihh(-/-) lines shows a substantial decrease in the expre

262 limited vascular remodeling observed in the Ihh(-/-) yolk sacs.

263 formation in the Runx2-null, but not in the Ihh-null embryo.

264 sely, a dominant negative Foxc1 inhibits the Ihh target gene expression.

265 wild-type and Ihh mutant vessels invade the Ihh(-/-) cartilage, though only wild-type vessels expand

266 ates of Evc(-/-) mice, but expression of the Ihh downstream genes Ptch1 and Gli1 was markedly decreas

267 We also suggest expression of the Ihh gene, which contains multiple Smad binding sites, mi

268 The BMP response element of the Ihh promoter contains multiple GC-rich motifs known as t

269 dral ossification was delayed in much of the Ihh(-/-) cranial bases but, surprisingly, was unaffected

270 mechanisms downstream or independent of the Ihh-PTHrP signaling pathway, a pivotal signaling system

271 ent manner, and have attempted to rescue the Ihh-null mouse with the Gli2 activator, either alone or

272 ous Ihh mRNA, and Atf4 directly binds to the Ihh promoter and activates its transcription.

273 ceptor Patched1 were present anterior to the Ihh-expressing secondary cartilage, proliferated, differ

274 aracterization of a mouse model in which the Ihh gene was successfully ablated from postnatal chondro

275 ation zone; this location coincides with the Ihh and Col X expression regions in vivo.

276 one of the growth plate, coinciding with the Ihh expression region in vivo.

277 the secondary chondrocytes derives from this Ihh source.

278 Thus, Ihh signaling is essential for symphyseal cartilage deve

279 o which different Gli proteins contribute to Ihh functions is not fully understood.

280 strated that these cells can also respond to Ihh, and do so both by enhanced proliferation and precoc

281 , a molecule necessary for responsiveness to Ihh, from the developing tendon and enthesis altered the

282 Equally unexpected, Ihh(-/-) growth plates stained poorly with Alcian blue a

283 ivated the beta-catenin gene and upregulated Ihh signaling simultaneously in the same cells during en

284 , exited from the cell cycle and upregulated Ihh.

285 e may both mediate the effect of upregulated Ihh signaling in promoting chondrocyte hypertrophy.

286 We found that upregulating Ihh signaling in the developing cartilage by treating PT

287 The early lethality of various Ihh-ablated mutant mice, however, prevented further anal

288 erence was seen in cultured wild-type versus Ihh(-/-) synchondrosis chondrocytes.

289 mbryos and continued Erg expression and weak Ihh expression in Sox5(-/-)6(-/-) growth plates suggest

290 yolk sacs deficient for Ihh or SMO: Whereas Ihh(-/-) yolk sacs can form blood vessels, the vessels a

291 In order to assess whether Ihh is sufficient to induce bone formation in vivo, we h

292 In order to determine whether Ihh is directly required for osteoblast differentiation,

293 vely by the pmx through a mechanism in which Ihh and Bmp4 synergize to promote expansion of bone tiss

294 y forming a negative feedback loop, in which Ihh signaling regulates chondrocyte hypertrophy by contr

295 collar in the long bones of embryos in which Ihh was artificially expressed in all chondrocytes by th

296 ressor is the predominant mode through which Ihh controls chondrocyte proliferation and maturation, b

297 Thus, the mechanism through which Ihh induces osteoblast differentiation requires other ef

298 lature-derived signal, which integrates with Ihh and Wnt signals to determine the osteoblast versus c

299 ed in vitro by periosteal cells treated with Ihh and BMP-2.

300 Rather than forming a typical narrow zone, Ihh(-/-) hypertrophic chondrocytes occupied an elongated