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.

Specific guidance of motor axons to duplicated muscles in the developing amniote limb

Development ◽  
1988 ◽  
Vol 103 (1) ◽  
pp. 97-110 ◽  
Author(s):  
R.V. Stirling ◽  
D. Summerbell
Keyword(s):  
Axon Guidance ◽  
Retrograde Transport ◽  
Positional Information ◽  
Limb Bud ◽  
Horse Radish Peroxidase ◽  
Change Position ◽  
Zone Of Polarizing Activity ◽  
Limb Pattern ◽  
Positional Value ◽  
Significant Support

The effect of alteration of limb pattern upon motor axon guidance has been investigated in chick embryos. Following grafting of the zone of polarizing activity (ZPA) into the anterior margin of the early limb bud, limbs develop with forearms duplicated about the anteroposterior axis. The position of motoneurones innervating the duplicated posterior forearm extensor EMU was mapped by retrograde transport of horse radish peroxidase (HRP). The motor pool labelled from injection into the anteriorly duplicated EMU muscle is consistently similar to that supplying the posterior EMU muscle on the unoperated side of the embryo. In those cases where the axons are well filled, their trajectories from the injection site are observed to change position within the radial nerve to specifically innervate the duplicated muscle. The axons modify their trajectories proximal to the level of limb duplication in a region where there is no change in the pattern of overt differentiation of the limb cells. This suggests that axons may use a cell's positional value to navigate and provides significant support for the theory of positional information.

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.

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.

Relationship between retinoic acid and sonic hedgehog, two polarizing signals in the chick wing bud

Development ◽  
1994 ◽  
Vol 120 (11) ◽  
pp. 3267-3274 ◽  
Author(s):  
J. Helms ◽  
C. Thaller ◽  
G. Eichele
Keyword(s):  
Retinoic Acid ◽  
Sonic Hedgehog ◽  
Positional Information ◽  
Limb Bud ◽  
Dependent Manner ◽  
All Trans Retinoic Acid ◽  
Wing Bud ◽  
Zone Of Polarizing Activity ◽  
Dose Dependent

Local application of all-trans-retinoic acid (RA) to the anterior margin of chick limb buds results in pattern duplications reminescent of those that develop after grafting cells from the zone of polarizing activity (ZPA). RA may act directly by conferring positional information to limb bud cells, or it may act indirectly by creating a polarizing region in the tissue distal to the RA source. Here we demonstrate that tissue distal to an RA-releasing bead acquires polarizing activity in a dose-dependent manner. Treatments with pharmacological (beads soaked in 330 micrograms/ml) and physiological (beads soaked in 10 micrograms/ml) doses of RA are equally capable of inducing digit pattern duplication. Additionally, both treatments induce sonic hedgehog (shh; also known as vertebrate hedgehog-1, vhh-1), a putative ZPA morphogen and Hoxd-11, a gene induced by the polarizing signal. However, tissue transplantation assays reveal that pharmacological, but not physiological, doses create a polarizing region. This differential response could be explained if physiological doses induced less shh than pharmacological doses. However, our in situ hybridization analyses demonstrate that both treatments result in similar amounts of mRNA encoding this candidate ZPA morphogen. We outline a model describing the apparently disparate effects of pharmacologic and physiological doses RA on limb bud tissue.

Retinoic acid induces a pattern of digits in anterior half wing buds that lack the zone of polarizing activity

Development ◽  
1989 ◽  
Vol 107 (4) ◽  
pp. 863-867 ◽  
Author(s):  
G. Eichele
Keyword(s):  
Retinoic Acid ◽  
Cell Fate ◽  
Anterior Margin ◽  
Limb Bud ◽  
Posterior Half ◽  
Anterior Half ◽  
Zone Of Polarizing Activity

Wing buds whose posterior half is excised, develop into wings lacking distal structures. However, such experimentally generated preaxial half wing buds can be rescued by implanting a retinoic-acid-releasing bead at their anterior margin. The polarity of the pattern that originates from preaxial half wing buds is reversed. For example, instead of a 234 digit pattern typical for normal wings, the order of digits is 432. This result implies that retinoic acid has the capacity to reprogram anterior limb bud tissue, and that the resulting change in cell fate does not depend on the presence of posterior tissue regions such as the zone of polarizing activity (ZPA).

Pattern formation along the anteroposterior axis of the chick wing: the increase in width following a polarizing region graft and the effect of X-irradiation

Development ◽  
1981 ◽  
Vol 63 (1) ◽  
pp. 127-144
Author(s):  
J. C. Smith ◽  
L. Wolpert
Keyword(s):  
Pattern Formation ◽  
Positional Information ◽  
Limb Bud ◽  
Anteroposterior Axis ◽  
X Irradiation ◽  
Host Embryo

A study is made of the widening of the chick limb bud that occurs after a graft of an additional polarizing region. Such buds are about 50% wider than controls, after 36 h. By contrast, growth along the proximodistal axis is unaffected. This widening is reduced by treating the host embryo with 10 Gy X-irradiation and the altered pattern of digits is consistent with a diffusible morphogen model for the specification of positional information along the anteroposterior axis.

Effects of biochemical inhibitors on positional signalling in the chick limb bud

Development ◽  
1981 ◽  
Vol 62 (1) ◽  
pp. 203-216
Author(s):  
Lawrence S. Honig ◽  
J. C. Smith ◽  
Amata Hornbruch ◽  
L. Wolpert
Keyword(s):  
Dna Synthesis ◽  
Rna Synthesis ◽  
Actinomycin D ◽  
Positional Information ◽  
Limb Bud ◽  
Limb Buds ◽  
Protein And Rna Synthesis ◽  
Zone Of Polarizing Activity ◽  
Rna And Dna Synthesis ◽  
Rna And Dna

In 3- to 4-day embryonic chick limb buds, a region at the posterior margin of the limb, the zone of polarizing activity, appears to be responsible for signalling positional information along the anteroposterior axis. Our experiments were designed to test which biosynthetic processes are required for polarizing activity. We have treated polarizing regions with biochemical inhibitors, and then assayed their abilities to induce limb reduplications when grafted into anterior sites on host limb buds, and also measured their capacities for protein, RNA, and DNA synthesis. DNA synthesis, and possibly oxidative phosphorylation, do not seem to be required for polarizing activity. But, glycolysis and protein and RNA synthesis are necessary, although not sufficient, for polarizing region activity. Activity seems particularly sensitive to inhibitors (actinomycin D and α-amanitin) of RNA synthesis.

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.

The control of growth and the development of pattern across the anteroposterior axis of the chick limb bud

Development ◽  
1981 ◽  
Vol 63 (1) ◽  
pp. 161-180
Author(s):  
Dennis Summerbell
Keyword(s):  
Diffusion Model ◽  
Growth Pattern ◽  
Mirror Image ◽  
Limb Bud ◽  
Limb Buds ◽  
Initial Distance ◽  
Anteroposterior Axis ◽  
Zone Of Polarizing Activity

Two grafts of zone of polarizing activity (ZPA) were made to host limb buds. The grafts define the width of the shared responding field lying between them. They cause a change in the growth pattern of the bud so that there is an increase in the width of the tissue between the grafts. Concurrently they redefine (respecify) cell states in the responding tissue so as to cause formation of a mirror-image reduplicate hand between them. The number and type of digits formed depends on the initial distance between the grafts. The results suggest that the initial presumptive hand field is very small (∼ 300µm), that it is not a classical morphallactic system, and that it is able to regulate its growth pattern. A pointsource diffusion model is presented.

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