Time, place and positional value in the chick limb-bud

Development ◽  
1975 ◽  
Vol 33 (3) ◽  
pp. 621-643
Author(s):  
D. Summerbell ◽  
J. H. Lewis
Keyword(s):  
Experimental Evidence ◽  
Long Range ◽  
Limb Development ◽  
Apical Ectodermal Ridge ◽  
Limb Bud ◽  
Timing Mechanism ◽  
Positional Value

Quantitative experimental evidence is presented for the progress zone theory of limb development. The theory, here formulated mathematically, states that the parts of the limb are specified in proximo-distal succession by an autonomous timing mechanism operating in a ‘progress zone’ of undifferentiated growing mesenchyme under the influence of the apical ectodermal ridge. By the exchange of distal tips between young and old wing-buds, it is shown that there are no long-range morphogenetic signals from proximal to distal tissue. The width of the progress zone is calculated, and it is found autoradiographically that practically all its cells are dividing.

A quantitative analysis of the effect of excision of the AER from the chick limb-bud

Development ◽  
1974 ◽  
Vol 32 (3) ◽  
pp. 651-660
Author(s):  
Dennis Summerbell
Keyword(s):  
Quantitative Analysis ◽  
Quantitative Method ◽  
Continuous Process ◽  
Apical Ectodermal Ridge ◽  
Rate Of Change ◽  
Limb Bud ◽  
Zone Model ◽  
Gradual Change ◽  
Analysis Of Results ◽  
Positional Value

The effect of removal of the apical ectodermal ridge from the early chick limb-bud is re-examined using a new quantitative method of analysis of results. The concept of the proximo-distal sequence of laying down of parts is confirmed and evidence is presented thatthis proceeds as a continuous process, there being a gradual change in the level specified from one cell to another at a more distal level. The results are then interpreted in terms of the ‘progress zone’ model to show that they are both consistent with the model and that they provide an assay for one of its parameters, the rate of change of positional value with time at the tip.

Retinoic acid signaling is required during early chick limb development

Development ◽  
1996 ◽  
Vol 122 (5) ◽  
pp. 1385-1394 ◽  
Author(s):  
J.A. Helms ◽  
C.H. Kim ◽  
G. Eichele ◽  
C. Thaller
Keyword(s):  
Retinoic Acid ◽  
Limb Development ◽  
Acid Synthesis ◽  
Apical Ectodermal Ridge ◽  
Limb Bud ◽  
Retinoid Receptor ◽  
Limb Morphogenesis ◽  
Wing Bud ◽  
Zone Of Polarizing Activity

In the chick limb bud, the zone of polarizing activity controls limb patterning along the anteroposterior and proximodistal axes. Since retinoic acid can induce ectopic polarizing activity, we examined whether this molecule plays a role in the establishment of the endogenous zone of polarizing activity. Grafts of wing bud mesenchyme treated with physiologic doses of retinoic acid had weak polarizing activity but inclusion of a retinoic acid-exposed apical ectodermal ridge or of prospective wing bud ectoderm evoked strong polarizing activity. Likewise, polarizing activity of prospective wing mesenchyme was markedly enhanced by co-grafting either a retinoic acid-exposed apical ectodermal ridge or ectoderm from the wing region. This equivalence of ectoderm-mesenchyme interactions required for the establishment of polarizing activity in retinoic acid-treated wing buds and in prospective wing tissue, suggests a role of retinoic acid in the establishment of the zone of polarizing activity. We found that prospective wing bud tissue is a high-point of retinoic acid synthesis. Furthermore, retinoid receptor-specific antagonists blocked limb morphogenesis and down-regulated a polarizing signal, sonic hedgehog. Limb agenesis was reversed when antagonist-exposed wing buds were treated with retinoic acid. Our results demonstrate a role of retinoic acid in the establishment of the endogenous zone of polarizing activity.

Interaction between the proximo-distal and antero-posterior co-ordinates of positional value during the specification of positional information in the early development of the chick limb-bud

Development ◽  
1974 ◽  
Vol 32 (1) ◽  
pp. 227-237
Author(s):  
Dennis Summerbell
Keyword(s):  
Early Development ◽  
Anterior Margin ◽  
Positional Information ◽  
Apical Ectodermal Ridge ◽  
Limb Bud ◽  
Anteroposterior Axis ◽  
Zone Of Polarizing Activity ◽  
Positional Value ◽  
Special Region

The experiments examine the extent of reduplication of skeletal parts across the anteroposterior axis, following the transplantation of a zone of polarizing activity (ZPA) to the anterior margin of the limb-bud at successively later stages. Previous studies have suggested that the function of the apical ectodermal ridge (AER) is to maintain cells in a special region at the distal tip (the progress zone) labile, with respect to their positional value along the proximo-distal axis. Similarly, the results of these experiments demonstrate that cells in the progress zone are able to change their antero-posterior positional value under the influence of the grafted ZPA, while cells at more proximal levels remain unaffected. In turn, the ZPA may effect the activity of the AER and hence the progress zone.

BMPR-IA signaling is required for the formation of the apical ectodermal ridge and dorsal-ventral patterning of the limb

Development ◽  
2001 ◽  
Vol 128 (22) ◽  
pp. 4449-4461 ◽  
Author(s):  
Kyung Ahn ◽  
Yuji Mishina ◽  
Mark C. Hanks ◽  
Richard R. Behringer ◽  
E. Bryan Crenshaw
Keyword(s):  
Limb Development ◽  
Apical Ectodermal Ridge ◽  
Bmp Signaling ◽  
Conditional Knockout ◽  
Limb Bud ◽  
Gene Encoding ◽  
Bone Morphogenetic Protein Receptor ◽  
Protein Receptor ◽  
Morphogenetic Protein ◽  
Embryonic Limb

We demonstrate that signaling via the bone morphogenetic protein receptor IA (BMPR-IA) is required to establish two of the three cardinal axes of the limb: the proximal-distal axis and the dorsal-ventral axis. We generated a conditional knockout of the gene encoding BMPR-IA (Bmpr) that disrupted BMP signaling in the limb ectoderm. In the most severely affected embryos, this conditional mutation resulted in gross malformations of the limbs with complete agenesis of the hindlimbs. The proximal-distal axis is specified by the apical ectodermal ridge (AER), which forms from limb ectoderm at the distal tip of the embryonic limb bud. Analyses of the expression of molecular markers, such as Fgf8, demonstrate that formation of the AER was disrupted in the Bmpr mutants. Along the dorsal/ventral axis, loss of engrailed 1 (En1) expression in the non-ridge ectoderm of the mutants resulted in a dorsal transformation of the ventral limb structures. The expression pattern of Bmp4 and Bmp7 suggest that these growth factors play an instructive role in specifying dorsoventral pattern in the limb. This study demonstrates that BMPR-IA signaling plays a crucial role in AER formation and in the establishment of the dorsal/ventral patterning during limb development.

scholarly journals Retinoids reprogramme pre-bud mesenchyme to give changes in limb pattern

Development ◽  
1987 ◽  
Vol 100 (4) ◽  
pp. 723-733 ◽  
Author(s):  
S.M. Wilde ◽  
S.E. Wedden ◽  
C. Tickle
Keyword(s):  
Retinoic Acid ◽  
Effective Treatment ◽  
Limb Development ◽  
Apical Ectodermal Ridge ◽  
Limb Bud ◽  
Chick Embryos ◽  
Early Stages ◽  
Limb Pattern

Retinoic acid was locally applied to presumptive limb regions of chick embryos to find out the earliest time at which the limb pattern can be reprogrammed. When beads soaked in retinoic acid were placed in the appropriate positions in embryos at stage 10 or older, duplicated or reduced leg patterns resulted. To pin point the time at which the cells in the limb rudiment respond to the retinoid, beads were removed at various times and the lengths of exposure required to reprogramme limb development found. The early limb rudiments require longer exposures to give duplications than late rudiments. The effective treatment periods last at least until stage 17 when the limb bud and apical ectodermal ridge develop. In contrast, the length of exposure to reduce the limb is constant at early stages. Retinoids first start acting to produce duplicated structures between stages 10 and 13. Therefore, retinoids appear to begin to reprogramme the cells as soon as they are determined to give rise to a limb.

Apical ridge dependent and independent mesodermal domains of GHox-7 and GHox-8 expression in chick limb buds

Development ◽  
1992 ◽  
Vol 116 (3) ◽  
pp. 811-818 ◽  
Author(s):  
M.A. Ros ◽  
G. Lyons ◽  
R.A. Kosher ◽  
W.B. Upholt ◽  
C.N. Coelho ◽  
...  
Keyword(s):  
Pattern Formation ◽  
Limb Development ◽  
Apical Ectodermal Ridge ◽  
Limb Bud ◽  
Rapid Decline ◽  
Limb Buds ◽  
Limb Outgrowth ◽  
Removal Experiments ◽  
The Relationship

The homeobox-containing genes GHox-7 and GHox-8 have been proposed to play fundamental roles in limb development. The expression of GHox-8, by the apical ridge cells, and GHox-7, in the subridge mesoderm, suggests the involvement of these two genes in limb outgrowth and proximo-distal pattern formation. A straightforward way to test this is to remove the apical ridge. Here we report the relationship between the mesodermal expression of GHox-7 and GHox-8 and the apical ectodermal ridge in the chick limb bud. The data from ridge removal experiments indicate that there are at least two domains of GHox-7 expression in the apical limb bud mesoderm. The posterior subridge GHox-7 domain in the progress zone requires the influence of the apical ridge for continued expression, while the anterior GHox-7 domain continues expression after ridge removal. Posterior subridge mesoderm is exquisitely sensitive to the loss of the ridge in that GHox-7 expression by these cells is reduced in only two hours and undetectable by three hours after ridge removal. It would appear that one of the ways progress zone cells respond to the apical ridge signal is by expressing GHox-7. The loss of ridge influence whether by growth at the apex or by ridge removal is followed by an unusually rapid decline in detectable GHox-7 transcripts. Maintenance of GHox-8 expression by the anterior mesoderm appears to be independent of the presence of the apical ridge.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Formin isoforms are differentially expressed in the mouse embryo and are required for normal expression of fgf-4 and shh in the limb bud

Development ◽  
1995 ◽  
Vol 121 (10) ◽  
pp. 3151-3162 ◽  
Author(s):  
D.C. Chan ◽  
A. Wynshaw-Boris ◽  
P. Leder
Keyword(s):  
Limb Development ◽  
Expression Patterns ◽  
Apical Ectodermal Ridge ◽  
Limb Bud ◽  
Amino Terminus ◽  
Ureteric Bud ◽  
Mrna Isoforms ◽  
Distal Limb ◽  
Limb Buds ◽  
Developing Kidney

Mice homozygous for the recessive limb deformity (ld) mutation display both limb and renal defects. The limb defects, oligodactyly and syndactyly, have been traced to improper differentiation of the apical ectodermal ridge (AER) and shortening of the anteroposterior limb axis. The renal defects, usually aplasia, are thought to result from failure of ureteric bud outgrowth. Since the ld locus gives rise to multiple RNA isoforms encoding several different proteins (termed formins), we wished to understand their role in the formation of these organs. Therefore, we first examined the embryonic expression patterns of the four major ld mRNA isoforms. Isoforms I, II and III (all containing a basic amino terminus) are expressed in dorsal root ganglia, cranial ganglia and the developing kidney including the ureteric bud. Isoform IV (containing an acidic amino terminus) is expressed in the notochord, the somites, the apical ectodermal ridge (AER) of the limb bud and the developing kidney including the ureteric bud. Using a lacZ reporter assay in transgenic mice, we show that this differential expression of isoform IV results from distinct regulatory sequences upstream of its first exon. These expression patterns suggest that all four isoforms may be involved in ureteric bud outgrowth, while isoform IV may be involved in AER differentiation. To define further the developmental consequences of the ld limb defect, we analyzed the expression of a number of genes thought to play a role in limb development. Most significantly, we find that although the AERs of ld limb buds express several AER markers, they do not express detectable levels of fibroblast growth factor 4 (fgf-4), which has been proposed to be the AER signal to the mesoderm. Thus we conclude that one or more formins are necessary to initiate and/or maintain fgf-4 production in the distal limb. Since ld limbs form distal structures such as digits, we further conclude that while fgf-4 is capable of supporting distal limb outgrowth in manipulated limbs, it is not essential for distal outgrowth in normal limb development. In addition, ld limbs show a severe decrease in the expression of several mesodermal markers, including sonic hedgehog (shh), a marker for the polarizing region and Hoxd-12, a marker for posterior mesoderm. We propose that incomplete differentiation of the AER in ld limb buds leads to reduction of polarizing activity and defects along the anteroposterior axis.

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.

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