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1 LPM induces ectodermal Fgf8 expression and a limb bud.
2 ic hedgehog (Shh) expression in the anterior limb bud.
3 n to promote Shh expression in the posterior limb bud.
4 ng to inhibit Shh expression in the anterior limb bud.
5 nication between cells within the developing limb bud.
6 oper patterning and growth of the developing limb bud.
7 at the apical ectodermal ridge (AER) of the limb bud.
8 anterior-posterior patterning of the amniote limb bud.
9 BMP4 represses Runx2 expression in the early limb bud.
10 he anterior-posterior axis of the vertebrate limb bud.
11 tic removal of several BMP activities in the limb bud.
12 ridge (AER) as a new signaling center in the limb bud.
13 og (Shh) mRNA to the posterior margin of the limb bud.
14 imiting Shh expression to the margins of the limb bud.
15 ecule Sonic Hedgehog (SHH) in the developing limb bud.
16 ShhN across the anteroposterior axis of the limb bud.
17 y promotes the spread of Shh gradient in the limb bud.
18 of the ZPA, is absent from the dolphin hind-limb bud.
19 ore posteriorly in the proximal third of the limb bud.
20 s widespread cell death within the embryonic limb bud.
21 cluding NCAM and collagen II (Col2a1) in the limb bud.
22 on of the skeletal architecture in the avian limb bud.
23 cells migrate from adjacent somites into the limb bud.
24 for the spatiotemporal control of Shh in the limb bud.
25 nt along which cells move to shape the early limb bud.
26 n the developing eye, pharyngeal arches, and limb bud.
27 sing on its regulation of Grem1 in the mouse limb bud.
28 ecific transcriptional activity in the mouse limb bud.
29 ate Shh expression at an ectopic site in the limb bud.
30 ntral nervous system, facial structures, and limb buds.
31 genes more frequently in male gonads than in limb buds.
32 velopment of the heart, branchial arches and limb buds.
33 the order observed in either mouse or chick limb buds.
34 al termination consistent with that in chick limb buds.
35 y reduced in the distal mesenchyme of mutant limb buds.
36 proximodistal axis in the early stage 19-22 limb buds.
37 e development of contralateral, un-amputated limb buds.
38 he basal state of appendage development from limb buds.
39 al insects produce appendages from embryonic limb buds.
40 -specific differentiation of Dicer-deficient limb buds.
41 d Fgf10 is nearly abolished in double mutant limb buds.
42 arlier, coinciding with the elongation of T3 limb buds.
43 an anencephalic head, spine, upper and lower limb buds.
44 s in mice such as somites, neural tubes, and limb buds.
45 cal ectodermal ridge (AER) of the developing limb buds.
46 transcriptional regulators required in early limb buds.
47 patterning and skeletal morphogenesis of the limb buds.
48 2 chromatin complexes from mouse embryos and limb buds.
49 h ligands to ectopic sites in the developing limb buds.
50 delamination and migration of cells into the limb buds.
51 e we show that during early outgrowth of the limb bud, a small cohort of cells express the orphan gen
52 ICM of the blastocyst, the myotomes, and the limb bud AER, is regulated by distinct enhancer elements
53 MO2 is also expressed in developing tail and limb buds, an expression pattern we now show to be recap
54 ed to ectopic Shh expression in the anterior limb bud and a preaxial polydactyly (PPD) skeletal pheno
56 FGF signaling regulates development of the limb bud and formation of the mesenchymal condensation a
57 hylome in RA FLS, we recently identified the limb bud and heart development (LBH) gene as a key dysre
58 ogenitor cells from different regions of the limb bud and identified unique cellular properties that
59 that developmental interactions between the limb bud and its innervation can be determinative for ad
60 expression to the proximal mesenchyme in the limb bud and later to chondrocytes associated with the f
61 ema to single-cell RNA-seq data from axolotl limb bud and limb regeneration stages shows that Polypte
62 establishes the anteroposterior axis of the limb bud and maintains proliferative expansion of limb e
63 ression of genes functioning in the proximal limb bud and orchestrates the establishment of anterior
64 (MPCs) have migrated from the somites to the limb bud and populated the prospective muscle masses.
65 surprisingly similar to that of the Xenopus limb bud and the zebrafish caudal fin, despite the diffe
66 pernumerary subclavian arteries in talpid(3) limb buds and abnormal expression of an artery-specific
67 is substantially restricted to the terminal limb buds and craniofacial processes during early develo
68 cription factors, expressed in the embryonic limb buds and ectoderm, are disease genes for these cond
70 ation sequencing (ChIP-seq) using developing limb buds and male gonads from embryos of two vertebrate
71 olecular dimorphisms between male and female limb buds and provide experimental evidence that the dig
72 expressed in central regions of early chick limb buds and proximal two thirds of later limbs, wherea
75 on for the loss of digit asymmetry in bovine limb buds and suggests that modifications affecting the
79 or role for this enhancer resides within the limb bud, and it serves to maintain a level of Tcfap2a e
80 ogenic lineage, located in the center of the limb bud, and soft connective tissue lineages located in
81 r and anterior regions of distal E10.5 mouse limb buds, and analysis in E10.5 dissected limb buds the
83 s comparable to its expression in developing limb buds, and it thus is an important marker for dediff
84 ally expressed in apoptotic regions of chick limb buds, and MafB/cFos heterodimers repressed apoptosi
87 BMP receptor gene Bmpr1a specifically in the limb bud apical ectodermal ridge (AER), a source of FGF
89 show that the mesenchymal cells of the early limb bud are not disorganized within the ectoderm as pre
92 ubpopulation of Myf5(+ve) progenitors in the limb buds at the late embryonic stage ( approximately E1
93 al epithelium of regenerating Xenopus laevis limb buds, at the appropriate time and place to play a r
95 onse of the flank could help ensure that the limb bud bulges out from, rather than becoming engulfed
96 e, does not regulate cell orientation in the limb bud but instead establishes a gradient of cell velo
97 hh expression in the posterior margin of the limb bud, but how this polarity is established is not cl
98 e Fgf4 for Fgf8 expression in the developing limb bud by concomitantly activating a conditional Fgf4
99 oss of Vhl in mesenchymal progenitors of the limb bud caused severe fibrosis of the synovial joints a
100 -function allele is activated in a wild-type limb bud causes formation of a supernumerary posterior d
102 on studies using micromass cultures of mouse limb bud cells further supported the conclusion that Cyp
103 raction profiles between proximal and distal limb bud cells isolated from mutant stocks where various
105 se results, Ddrgk1-/- mice displayed delayed limb bud chondrogenic condensation, decreased SOX9 prote
106 oreover, expression of SoxB1 proteins in the limb bud confers on mesodermal cells the potential to ac
107 s of MafB, cFos and cJun in developing chick limb buds control the number of apoptotic cells, and tha
108 ein in the posterior mesenchyme of the mouse limb bud correlates with a long-range chromatin interact
109 We found that premature AER loss in mutant limb buds delayed generation of autopod progenitors, whi
110 ra, sometimes multiple digits, from anterior limb bud demonstrating the negative role in Shh signalin
111 atory module at the time and place of distal limb bud development when the GCR participates in initia
112 P-D-patterning gene expression during early limb bud development, providing genetic evidence that AE
122 egulated in the proximal central core of the limb bud during the formation of the precartilage conden
124 eles were removed either from the developing limb bud ectoderm (using Msx2-Cre) or from the mesenchym
125 it has been stated that Hh signaling in the limb bud ectoderm cannot occur because components of the
126 etic ablation of Rac1 in the mouse embryonic limb bud ectoderm disrupts canonical Wnt signaling and p
137 with elevated expression in the prospective limb bud field, is capable of inhibiting Hand2/Tbx3 expr
140 Although numerous molecules required for limb bud formation have recently been identified, the mo
142 of expression in the hindlimb field, during limb bud formation, alters neither limb outgrowth nor ex
145 Our data indicate that the cetacean hind-limb bud forms an AER and that this structure expresses
146 pression at the distal edge of the embryonic limb bud, forms abnormally in the absence of Megf7.
149 d more frequently in SOX9 binding regions in limb bud genes compared with those in male gonad genes.
154 number and volume density differences: 4-day limb buds had 2- to 2.5-fold as many cells per unit area
156 For more than a century, the vertebrate limb bud has served as a model for studying cell signall
157 on tibial pioneer neurons in the developing limb bud have been well characterized in the grasshopper
160 to restrict Shh expression to the posterior limb bud, how they function together remains unclear.
162 for appropriate muscle development in chick limb buds; however, Fgfr4 null mice show no phenotype.
163 find that upon ectopic expression in distal limb buds, HOXA11 binds sites normally HOX13-specific.
164 eleted VHL in mesenchymal progenitors of the limb bud, i.e. in cells not yet committed to the chondro
165 atin immunoprecipitation sequencing in chick limb buds identified potential target genes and regulato
166 fers a first step for creating an artificial limb bud in culture and might open the door to inducing
167 ression of Has2 in the mesoderm of the chick limb bud in vivo results in the formation of shortened a
169 f Engrailed-1 (En1) expression in the AER of limb buds in which Bmp2 and Bmp4 had been removed indica
170 on only in the Shh-expressing regions of the limb bud, in a conformation consistent with enhancer-pro
172 n of chondrocyte progenitors in the proximal limb-bud independently of known P-D patterning markers a
173 ipitation of DNA-Gli3 protein complexes from limb buds indicated that Gli3 strongly binds to the Has2
174 is expressed in the distal mesenchyme of the limb bud, induces premature expression of both Myf5 and
176 , including limb positioning (Hoxc6, Hoxd9), limb bud initiation (Pitx1, Tbx4, Tbx5), and limb bud ou
180 of myogenic cells from the somites into the limb bud is followed by their extension from the proxima
183 location on the surface of the middle of the limb bud is sufficient to induce ectopic expression of T
187 g region, at the posterior of the vertebrate limb bud, is pivotal in determining digit number and ide
188 l ligands may be expressed in the developing limb bud, it was possible that loss of Jagged2 disabled
190 imb development starts with the formation of limb buds (LBs), which consist of tissues from two diffe
191 ed BMP signaling in the mesoderm between the limb buds leads to abnormal somite differentiation and a
192 gestation in a proximal-dorsal region of the limb bud, leads to the elimination of enough mesenchymal
193 abrogates ectopic Shh expression in anterior limb buds, limits overexpression in the zone of polarizi
195 analysis system to track the fate of single limb bud mesenchymal cells at different times in early l
196 er (R26R) mice revealed that Sox9-expressing limb bud mesenchymal cells gave rise to both chondrocyte
199 y)-cre line led to Fgfr1 inactivation in all limb bud mesenchyme (LBM) cells during limb initiation.
200 is expressed and transcriptionally active in limb bud mesenchyme and in mesenchymal condensations.
201 e associated with decreased proliferation of limb bud mesenchyme and small cartilaginous condensation
202 t severely impairs Tcfap2a expression in the limb bud mesenchyme but generates only a modest reductio
203 terior and posterior polarity of the nascent limb bud mesenchyme by impacting Gli3 and Tbx3 expressio
206 8 function in the forelimb AER, we show that limb bud mesenchyme fails to survive in the absence of b
207 ent, and its conditional deletion from early limb bud mesenchyme in mice severely affects both initia
208 ing the Cre/loxP system in mice, we rendered limb bud mesenchyme insensitive to BMP signals through t
209 , we conditionally inactivated Hif-1alpha in limb bud mesenchyme using a Prx1 promoter-driven Cre tra
211 is dynamically expressed in the early distal limb bud mesenchyme, with expression becoming downregula
216 es, it has been shown that activation in the limb bud mesoderm is required for normal limb developmen
217 tivated the gene for HA synthase 2, Has2, in limb bud mesoderm using mice that harbor a floxed allele
220 ucleotides to manipulate Barx2 expression in limb bud micromass cultures, we determined that Barx2 is
221 using several mammalian cell lines and chick limb bud micromass cultures, we determined that mutant R
224 ed light on the cellular basis of vertebrate limb bud morphogenesis and uncover new layers to the seq
225 findings imply that IRX3/5 coordinate early limb bud morphogenesis with skeletal pattern formation.
227 ng limb, and Northern blot analysis of chick limb bud mRNA shows that APBP-1 mRNA expression is inver
228 we provide evidence that Msx1 expression in limb bud muscle precursor cells is dependent on the cano
231 drives the proximal-distal elongation of the limb bud necessary to set the stage for subsequent morph
238 does not regulate myogenic initiation in the limb bud or maintenance in the first or second branchial
242 Together with previous lineage studies of limb buds, our results indicate that, at the pelvic leve
244 limb bud initiation (Pitx1, Tbx4, Tbx5), and limb bud outgrowth (Shh, Fgf10), and studied their expre
246 icle morphogenesis as well as the AER during limb bud outgrowth in humans, whereas it is not required
248 revealed an obligatory role for COUP-TFII in limb bud outgrowth since mutant cells are unable to cont
249 to play a critical role in the initiation of limb bud outgrowth via restriction of Fgf10 expression t
252 t to be a key signaling molecule involved in limb bud patterning along the proximodistal or anteropos
254 ist1 activity thresholds contribute to early limb bud patterning, and suggest how particular combinat
257 cellular automaton model for the behavior of limb bud precartilage mesenchymal cells undergoing chond
258 pattern formation, IRX3/5 help to shape the limb bud primordium by promoting the separation and inte
260 n the posterior mesenchyme of the developing limb bud regulates patterning and growth of the developi
263 tissue and molecular interactions within the limb bud required for patterning and morphogenesis of th
268 romosome conformation capture from embryonic limb buds showed that the enhancer cluster activated sev
272 correlates with the spatiotemporal domain of limb bud-specific Shh expression, but close Shh and ZRS
274 trongly expressed in the pharyngeal arch and limb bud, supporting a site- and stage-specific requirem
275 d distal regions of genes more frequently in limb buds than in male gonads, while SOX9 bound to the p
276 is a secreted molecule made in the posterior limb bud that affects patterning and development of mult
278 ubapical mesenchymal cells of the developing limb bud that are undergoing proliferation, directed mig
279 ide evidence from mouse conditional knockout limb buds that the bHLH family transcription factor gene
280 hin neighboring subregions of the developing limb bud, the compound patterns did not show signs of cr
281 primitive mesenchymal cells of the embryonic limb bud, the EF mice were noted to have a number of dev
282 sitioning of the limbs, the formation of the limb bud, the establishment of the principal limb axes,
284 e critical signaling center of the posterior limb bud, the Zone of Polarizing Activity (ZPA), as has
285 gl2 alters the shape and dimensions of early limb buds: the width and thickness are increased, wherea
286 e limb buds, and analysis in E10.5 dissected limb buds themselves, we show that there is a loss of po
287 ating and extending axons to the base of the limb bud, they display spontaneous, highly rhythmic, and
288 lock in polarizing region cells of the chick limb bud times the duration of Sonic hedgehog (Shh) expr
290 odermal ridge (AER) at the distal tip of the limb bud to direct outgrowth along the proximal to dista
291 uced by this effect will cause the incipient limb bud to phase separate from the surrounding flank, w
293 ic expression of Chrdl1 throughout the avian limb bud using viral misexpression resulted in an oligod
294 idge (AER) at the distal tip of the tetrapod limb bud was shown to produce signals necessary for deve
295 ressed in the apical ectodermal ridge in the limb bud, we demonstrate that the Fgf9-/- limb phenotype
296 expression to the marginal mesenchyme of the limb bud, we undertook a series of grafting and extirpat
297 ssues including, classically, the developing limb bud where it controls digit number and identity.
298 e of limb level somites and migrate into the limb bud where they form the dorsal and ventral muscle m