scholarly journals COINCINDENT ACTIVATION OF THE WNT AND SHH PATHWAYS BY FGF IN THE POSTERIOR LIMB BUD

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Jonathan M Van Arsdale ◽  
Jennifer M Feenstra ◽  
Charmaine U Pira ◽  
Kerby C Oberg
Keyword(s):  
Limb Bud ◽  
Posterior Limb

FGF-4 maintains polarizing activity of posterior limb bud cells in vivo and in vitro

Development ◽  
1993 ◽  
Vol 119 (1) ◽  
pp. 199-206 ◽  
Author(s):  
A. Vogel ◽  
C. Tickle
Keyword(s):  
Posterior Margin ◽  
Anterior Margin ◽  
Marked Decrease ◽  
Mesenchymal Cells ◽  
Apical Ectodermal Ridge ◽  
Limb Bud ◽  
Posterior Limb ◽  
Vertebrate Limb

The polarizing region is a major signalling tissue involved in patterning the tissues of the vertebrate limb. The polarizing region is located at the posterior margin of the limb bud and can be recognized by its ability to induce additional digits when grafted to the anterior margin of a chick limb bud. The signal from the polarizing region operates at the tip of the bud in the progress zone, a zone of undifferentiated mesenchymal cells, maintained by interactions with the apical ectodermal ridge. A number of observations have pointed to a link between the apical ectodermal ridge and signalling by the polarizing region. To test this possibility, we removed the posterior apical ectodermal ridge of chick wing buds and assayed posterior mesenchyme for polarizing activity. When the apical ectodermal ridge is removed, there is a marked decrease in polarizing activity of posterior cells. The posterior apical ectodermal ridge is known to express FGF-4 and we show that the decrease in polarizing activity of posterior cells of wing buds that normally follows ridge removal can be prevented by implanting a FGF-4-soaked bead. Furthermore, we show that both ectoderm and FGF-4 maintain polarizing activity of limb bud cells in culture.

Evidence that members of the Cut/Cux/CDP family may be involved in AER positioning and polarizing activity during chick limb development

Development ◽  
2000 ◽  
Vol 127 (23) ◽  
pp. 5133-5144
Author(s):  
A.T. Tavares ◽  
T. Tsukui ◽  
J.C. Izpisua Belmonte
Keyword(s):  
Limb Development ◽  
Limb Bud ◽  
Wing Margin ◽  
Lateral Plate ◽  
Posterior Limb ◽  
Downstream Target ◽  
Notch Pathways ◽  
Specialized Region ◽  
Dorsoventral Boundary ◽  
Cycle Regulation

In vertebrates, the apical ectodermal ridge (AER) is a specialized epithelium localized at the dorsoventral boundary of the limb bud that regulates limb outgrowth. In Drosophila, the wing margin is also a specialized region located at the dorsoventral frontier of the wing imaginal disc. The wingless and Notch pathways have been implicated in positioning both the wing margin and the AER. One of the nuclear effectors of the Notch signal in the wing margin is the transcription factor cut. Here we report the identification of two chick homologues of the Cut/Cux/CDP family that are expressed in the developing limb bud. Chick cux1 is expressed in the ectoderm outside the AER, as well as around ridge-like structures induced by (β)-catenin, a downstream target of the Wnt pathway. cux1 overexpression in the chick limb results in scalloping of the AER and limb truncations, suggesting that Cux1 may have a role in limiting the position of the AER by preventing the ectodermal cells around it from differentiating into AER cells. The second molecule of the Cut family identified in this study, cux2, is expressed in the pre-limb lateral plate mesoderm, posterior limb bud and flank mesenchyme, a pattern reminiscent of the distribution of polarizing activity. The polarizing activity is determined by the ability of a certain region to induce digit duplications when grafted into the anterior margin of a host limb bud. Several manipulations of the chick limb bud show that cux2 expression is regulated by retinoic acid, Sonic hedgehog and the posterior AER. These results suggest that Cux2 may have a role in generating or mediating polarizing activity. Taking into account the probable involvement of Cut/Cux/CDP molecules in cell cycle regulation and differentiation, our results raise the hypothesis that chick Cux1 and Cux2 may act by modulating proliferation versus differentiation in the limb ectoderm and polarizing activity regions, respectively.

scholarly journals Ectopic Expression ofMsx-2in Posterior Limb Bud Mesoderm Impairs Limb Morphogenesis While InducingBMP-4Expression, Inhibiting Cell Proliferation, and Promoting Apoptosis

1998 ◽  
Vol 197 (1) ◽  
pp. 12-24 ◽  
Author(s):  
Deborah Ferrari ◽  
Alexander C. Lichtler ◽  
ZhongZong Pan ◽  
Caroline N. Dealy ◽  
William B. Upholt ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Ectopic Expression ◽  
Limb Bud ◽  
Posterior Limb ◽  
Limb Morphogenesis

scholarly journals Intercalation and the cellular origin of supernumerary limbs in Xenopus

Development ◽  
1987 ◽  
Vol 99 (4) ◽  
pp. 521-526 ◽  
Author(s):  
K. Muneoka ◽  
E.H. Murad
Keyword(s):  
Limb Development ◽  
Limb Bud ◽  
Posterior Limb ◽  
Cellular Origin ◽  
Supernumerary Limbs ◽  
Anterior Posterior ◽  
Anterior Posterior Axis

The hypothesis that a specialized polarizing zone controls the pattern of the anterior-posterior axis during limb development in Xenopus has been tested by analysing the cellular contribution to supernumerary limbs. Supernumerary limbs were generated by grafting hindlimb buds contralaterally between X. borealis and X. laevis to appose anterior and posterior limb tissues. Cells derived from these two species of Xenopus are readily identified by staining with quinacrine. The analysis of cellular contribution showed that supernumerary limbs consist of approximately half anterior-derived (57%) and half posterior-derived (43%) cells. These data are not consistent with the polarizing zone theory but are consistent with the hypothesis that both supernumerary limbs and normally developing limbs arise from intercalary interactions between limb bud cells with different positional values.

Evidence that preaxial polydactyly in the Doublefoot mutant is due to ectopic Indian Hedgehog signaling

Development ◽  
1998 ◽  
Vol 125 (16) ◽  
pp. 3123-3132 ◽  
Author(s):  
Y. Yang ◽  
P. Guillot ◽  
Y. Boyd ◽  
M.F. Lyon ◽  
A.P. McMahon
Keyword(s):  
Hedgehog Signaling ◽  
Interspecific Backcross ◽  
Limb Bud ◽  
Chromosome 1 ◽  
Indian Hedgehog ◽  
Posterior Limb ◽  
Preaxial Polydactyly ◽  
Ectopic Activation ◽  
Zone Of Polarizing Activity ◽  
Anterior Posterior

Patterning of the vertebrate limb along the anterior-posterior axis is controlled by the zone of polarizing activity (ZPA) located at the posterior limb margin. One of the vertebrate Hh family members, Shh, has been shown to be able to mediate the function of the ZPA. Several naturally occurring mouse mutations with the phenotype of preaxial polydactyly exhibit ectopic Shh expression at the anterior limb margin. In this study, we report the molecular characterization of a spontaneous mouse mutation, Doublefoot (Dbf). Dbf is a dominant mutation which maps to chromosome 1. Heterozygous and homozygous embryos display a severe polydactyly with 6 to 8 digits on each limb. We show here that Shh is expressed normally in Dbf mutants. In contrast, a second Hh family member, Indian hedgehog (Ihh) which maps close to Dbf, is ectopically expressed in the distal limb bud. Ectopic Ihh expression in the distal and anterior limb bud results in the ectopic activation of several genes associated with anterior-posterior and proximal-distal patterning (Fgf4, Hoxd13, Bmp2). In addition, specific components in the Hedgehog pathway are either ectopically activated (Ptc, Ptc-2, Gli1) or repressed (Gli2). We propose that misexpression of Ihh, and not a novel Smoothened ligand as recently suggested (Hayes et al., 1998), is responsible for the Dbf phenotype. We consider that Ihh has a similar activity to Shh when expressed in the early Shh-responsive limb bud. To determine whether Dbf maps to the Ihh locus, which is also on chromosome 1, we performed an interspecific backcross. These results demonstrate that Dbf and Ihh are genetically separated by approximately 1.3 centimorgans, suggesting that Dbf mutation may cause an exceptionally long-range disruption of Ihh regulation. Although this leads to ectopic activation of Ihh, normal expression of Ihh in the cartilaginous elements is retained.

BMP signaling during bone pattern determination in the developing limb

Development ◽  
1996 ◽  
Vol 122 (11) ◽  
pp. 3557-3566 ◽  
Author(s):  
Y. Kawakami ◽  
T. Ishikawa ◽  
M. Shimabara ◽  
N. Tanda ◽  
M. Enomoto-Iwamoto ◽  
...  
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Kinase Domain ◽  
Distal Region ◽  
Bmp Signaling ◽  
Dominant Negative ◽  
Limb Bud ◽  
Type I ◽  
Posterior Limb ◽  
Receptor Complexes ◽  
Limb Mesenchyme

To examine the role of BMP signaling during limb pattern formation, we isolated chicken cDNAs encoding type I (BRK-1 and BRK-2) and type II (BRK-3) receptors for bone morphogenetic proteins. BRK-2 and BRK-3, which constitute dual-affinity signaling receptor complexes for BMPs, are co-expressed in condensing precartilaginous cells, while BRK-1 is weakly expressed in the limb mesenchyme. BRK-3 is also expressed in the apical ectodermal ridge and interdigital limb mesenchyme. BRK-2 is intensely expressed in the posterior-distal region of the limb bud. During digit duplication by implanting Sonic hedgehog-producing cells, BRK-2 expression is induced anteriorly in the new digit forming region as observed for BMP-2 and BMP-7 expression in the limb bud. Dominant-negative effects on BMP signaling were obtained by over-expressing kinase domain-deficient forms of the receptors. Chondrogenesis of limb mesenchymal cells is markedly inhibited by dominant-negative BRK-2 and BRK-3, but not by BRK-1. Although the bone pattern was not disturbed by expressing individual dominant-negative BRK independently, preferential distal and posterior limb truncations resulted from co-expressing the dominant-negative forms of BRK-2 and BRK-3 in the whole limb bud, thus providing evidence that BMPs are essential morphogenetic signals for limb bone patterning.

The target tissue of limb-bud polarizing activity in the induction of supernumerary structures

Development ◽  
1979 ◽  
Vol 53 (1) ◽  
pp. 67-73
Author(s):  
Jeffrey A. Maccabe ◽  
Brenda W. Parker
Keyword(s):  
Limb Bud ◽  
Target Tissue ◽  
Posterior Border ◽  
Posterior Limb ◽  
Anteroposterior Axis

When polarizing mesoderm from the posterior border of the 4-day chick limb bud is placed adjacent to anterior limb mesoderm and ectodermal ridge, the anterior ridge thickens and mesodermal outgrowth ensues, resulting in supernumerary limb structures. This apposition of anterior and posterior limb tissues can be accomplished by cutting off the apical one third of the limb bud and reimplanting it on the stump with its anteroposterior axis reversed. The preaxial response to polarizing activity can be obtained after only 12–18 h in the reoriented position. Reversed apical mesoderm develops supernumerary digits when combined with untreated ectoderm. The reciprocal combination, reversed ectoderm and untreated mesoderm, fails to develop supernumerary structures. We have interpreted this as evidence that, in inducing supernumerary limb structures, polarizing activity actsonly on the mesoderm.

scholarly journals Regulation of Gremlin expression in the posterior limb bud

2006 ◽  
Vol 299 (1) ◽  
pp. 12-21 ◽  
Author(s):  
Sahar Nissim ◽  
Sean M. Hasso ◽  
John F. Fallon ◽  
Clifford J. Tabin
Keyword(s):  
Limb Bud ◽  
Posterior Limb

The origin and movement of the limb-bud epithelium and mesenchyme in the chick embryo as determined by radioautographic mapping

Development ◽  
1971 ◽  
Vol 25 (1) ◽  
pp. 85-96
Author(s):  
Glenn C. Rosenquist
Keyword(s):  
Primitive Streak ◽  
Limb Bud ◽  
Lateral Margin ◽  
Lateral Plate ◽  
Posterior Limb ◽  
Process Stage ◽  
The Future ◽  
Dorsal Portion ◽  
Definition Of ◽  
Area Pellucida

The origin of the limb-bud cells was determined by tracing the movements of [3H]thymidine-labelled grafts excised from late medium-streak to 5-somite stage chick embryos and transplanted to the epiblast, streak, and endoderm-mesoderm of similarly staged recipient embryos. Although exact definition of the prelimb areas was not possible because of the small number of grafts placed at each developmental stage, the study showed in general that at the late medium-streak stage the future limb-bud epithelium is in the epiblast (dorsal) layer near the lateral margin of the area pellucida. It moves medially toward the embryonic axis, just lateral to the premesoderm cells which will be invaginated at the primitive streak. With regression of the streak, the limb-bud epithelium moves relatively anteriorly into a position dorsal to the limb-bud mesoderm, beginning at least as early as the early head-fold stage. At the definitive-streak stage, the future limb-bud mesoderm is in the epiblast layer about halfway from the streak to the lateral margin of the area pellucida, at a level about halfway between the anterior and posterior ends of the streak. From this position the prelimb mesoderm migrates medially to the streak, and is invaginated into the mesoderm layer at a position about halfway between the anterior and posterior ends of the streak; after the head-process stage, it migrates anteriorly and laterally into the somatic layer of the lateral plate, ventral to the limb-bud epithelium. Mesoderm which will form the anterior limb-bud migrates anterior to mesoderm which will form the posterior limb-bud; mesoderm which will form the ventral portion of each limb-bud migrates posterolateral to mesoderm which will form the dorsal portion of each limb-bud.

The role of gap junctions in patterning of the chick limb bud

Development ◽  
1990 ◽  
Vol 108 (4) ◽  
pp. 623-634 ◽  
Author(s):  
F. Allen ◽  
C. Tickle ◽  
A. Warner
Keyword(s):  
Gap Junctions ◽  
Lucifer Yellow ◽  
Limb Bud ◽  
Limb Patterning ◽  
Posterior Limb ◽  
Gap Junctional Communication ◽  
Junctional Communication ◽  
Mesenchyme Cells ◽  
Gap Junctional

The role of gap junctional communication during patterning of the chick limb has been investigated. Affinity-purified antibodies raised against rat liver gap junctional proteins were used to block communication between limb mesenchyme cells. Co-injection of the antibodies and Lucifer yellow into mesenchyme cultures demonstrated that communication was inhibited almost immediately. When antibodies were loaded into mesenchyme tissue by DMSO permeabilization, [3H]nucleotide transfer was prevented for at least 16 h. Polarizing region tissue from the posterior limb bud margin causes digit duplications when grafted to the anterior margin. Quail polarizing region cells were loaded with gap junction antibody and grafted into chick wing buds. The antibody had no effect on growth or survival of the grafted cells. As very few polarizing region cells are required to initiate duplications, the number of polarizing region cells in the grafts was reduced by diluting 1:9 with anterior mesenchyme tissue. When either polarizing region or anterior mesenchyme tissue in the graft was loaded separately with antibody, there was little effect on respecification of the digit pattern. However, loading both tissues in the graft caused a significant decrease in duplications. This indicates that a major role of gap junctions in limb patterning may be to enable polarizing region cells to communicate directly with adjacent anterior mesenchyme. A role for gap junctional communication between anterior mesenchyme cells cannot be excluded. The results are discussed in relation to the role of retinoic acid as a putative morphogen.

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