The effect of cell killing by X-irradiation on pattern formation in the chick limb

Development ◽  
1979 ◽  
Vol 50 (1) ◽  
pp. 175-198
Author(s):  
L. Wolpert ◽  
C. Tickle ◽  
M. Sampford ◽  
J. H. Lewis
Keyword(s):  
Quantitative Analysis ◽  
Pattern Formation ◽  
Positional Information ◽  
Limb Bud ◽  
Zone Model ◽  
Viable Cells ◽  
Dividing Cells ◽  
X Irradiation ◽  
Mesenchyme Cells ◽  
Number Of Cells

It has been suggested that positional information along the proximo-distal axis of the limb-bud is specified by time spent in the progress zone. Mesenchyme cells have been killed by X-irradiation, reducing the rate cells leave the zone. The time spent there by some cells is thus increased. When limbs, stage 18/19, stage 21, or tips of stage 24, are treated with increasing doses of X-irradiation, from 1000 rads to 2500 rads proximal structures are progressively lost, whereas distal ones— the digits—are relatively unaffected. There was no evidence for intercalation of missing parts. These effects are due to killing or damage of mesenchyme cells: the ectoderm is not affected at these doses. The results are consistent with a quantitative analysis based on the progress zone model, in which viable cells repopulate the progress zone and gradually restore it to normal as non-dividing cells are diluted out. It is suggested that any treatment causing damage to the mesenchyme at early stages will give similar results. The mesenchyme cells appear to be surprisingly resistant to radiation damage. The form of the limb-bud is not altered by damaging the mesenchyme. Differences in the development of structures at similar proximo-distal levels, following irradiation, is considered in terms of the requirement of a threshold number of cells.

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.

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 and chick limb bud development

Development ◽  
1991 ◽  
Vol 113 (Supplement_1) ◽  
pp. 113-121 ◽  
Author(s):  
C. Tickle
Keyword(s):  
Retinoic Acid ◽  
Target Genes ◽  
Homeobox Gene ◽  
Experimental System ◽  
Shoulder Girdle ◽  
Limb Bud ◽  
Local Concentration ◽  
Anterior Position ◽  
Mesenchyme Cells ◽  
Vitamin A Derivative

The chick limb bud is a powerful experimental system in which to study pattern formation in vertebrate embryos. Exogenously applied retinoic acid, a vitamin A derivative, can bring about changes in pattern and, on several grounds, is a good candidate for an endogenous morphogen. As such, the local concentration of retinoic acid might provide cells with information about their position in relation to one axis of the limb. Alternatively, retinoic acid may be part of a more complex signalling system. Homeobox genes are possible target genes for regulation by retinoic acid in the limb. In particular, one homeobox gene, XlHbox 1 is expressed locally in the mesenchyme of vertebrate forelimbs and might code for an anterior position. When the pattern of the chick wing is changed by retinoic acid or by grafts of signalling tissue such that anterior cells now form posterior structures, the domain of XlHbox 1 expression expands rather than contracts. The expansion of XlHbox 1 expression correlates with shoulder girdle abnormalities. Retinoic acid application leads to visible changes in bud shape and this allows dissection of the way in which patterning is co-ordinated with morphogenesis. Results of recombination experiments and studies of changes in the apical ridge and proliferation in the mesenchyme suggest the following scheme: retinoic acid is involved in specification of position of mesenchyme cells; this specification determines their local interaction with the ridge that controls ridge morphology; the thickened apical ridge permits local proliferation in the underlying mesenchyme. The recent advances in molecular biology that permit analysis of the expression of various interesting genes in developing limbs hold out the promise that further investigation may soon allow a complete account of the patterning process in one part of the vertebrate embryo.

The application of aqueous two-phase partition to the study of chick limb mesenchymal diversification

Development ◽  
1986 ◽  
Vol 94 (1) ◽  
pp. 267-275
Author(s):  
C. P. Cottrill ◽  
Paul T. Sharpe ◽  
Lewis Wolpert
Keyword(s):  
Pattern Formation ◽  
Limb Development ◽  
Developmental Stages ◽  
Proximal Region ◽  
Limb Bud ◽  
Cell Populations ◽  
Two Phase ◽  
Phase Partition ◽  
Surface Character ◽  
Two Phase Partition

A technique which identifies cells differing in surface character, aqueous two-phase partition using thin-layer countercurrent distribution (TLCCD), has been used to study differentiation and pattern formation in the developing chick limb bud. The TLCCD profiles of cell populations, derived from various regions of morphologically undifferentiated mesenchyme from three different stages of limb development, have been compared. At no stage, or location, has the population been found to be homogeneous. Cells from progress zones and more proximal regions could all be resolved into several populations. The populations from progress zones at three different developmental stages were qualitatively similar but differed in the proportions of cells in each. The most striking differences in cell populations were those obtained from the most proximal region of the limb, closest to the flank, which represents the developmentally most advanced region.

The dominant hemimelia mutation uncouples epithelial-mesenchymal interactions and disrupts anterior mesenchyme formation in mouse hindlimbs

Development ◽  
1999 ◽  
Vol 126 (21) ◽  
pp. 4729-4736
Author(s):  
L. Lettice ◽  
J. Hecksher-Sorensen ◽  
R.E. Hill
Keyword(s):  
Gene Expression ◽  
Pattern Formation ◽  
Limb Development ◽  
Limb Bud ◽  
Mouse Mutation ◽  
Number Of Factors ◽  
Limb Outgrowth ◽  
Gene Functions ◽  
Regulatory Loop ◽  
Limb Initiation

Epithelial-mesenchymal interactions are essential for both limb outgrowth and pattern formation in the limb. Molecules capable of communication between these two tissues are known and include the signaling molecules SHH and FGF4, FGF8 and FGF10. Evidence suggests that the pattern and maintenance of expression of these genes are dependent on a number of factors including regulatory loops between genes expressed in the AER and those in the underlying mesenchyme. We show here that the mouse mutation dominant hemimelia (Dh) alters the pattern of gene expression in the AER such that Fgf4, which is normally expressed in a posterior domain, and Fgf8, which is expressed throughout are expressed in anterior patterns. We show that maintenance of Shh expression in the posterior mesenchyme is not dependent on either expression of Fgf4 or normal levels of Fgf8 in the overlying AER. Conversely, AER expression of Fgf4 is not directly dependent on Shh expression. Also the reciprocal regulatory loop proposed for Fgf8 in the AER and Fgf10 in the underlying mesenchyme is also uncoupled by this mutation. Early during the process of limb initiation, Dh is involved in regulating the width of the limb bud, the mutation resulting in selective loss of anterior mesenchyme. The Dh gene functions in the initial stages of limb development and we suggest that these initial roles are linked to mechanisms that pattern gene expression in the AER.

scholarly journals An intrinsic cell cycle timer terminates limb bud outgrowth

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Joseph Pickering ◽  
Constance A Rich ◽  
Holly Stainton ◽  
Cristina Aceituno ◽  
Kavitha Chinnaiya ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Rna Sequencing ◽  
Late Stage ◽  
Limb Development ◽  
Limb Bud ◽  
Limb Outgrowth ◽  
Bmp Signalling ◽  
Mesenchyme Cells

The longstanding view of how proliferative outgrowth terminates following the patterning phase of limb development involves the breakdown of reciprocal extrinsic signalling between the distal mesenchyme and the overlying epithelium (e-m signalling). However, by grafting distal mesenchyme cells from late stage chick wing buds to the epithelial environment of younger wing buds, we show that this mechanism is not required. RNA sequencing reveals that distal mesenchyme cells complete proliferative outgrowth by an intrinsic cell cycle timer in the presence of e-m signalling. In this process, e-m signalling is required permissively to allow the intrinsic cell cycle timer to run its course. We provide evidence that a temporal switch from BMP antagonism to BMP signalling controls the intrinsic cell cycle timer during limb outgrowth. Our findings have general implications for other patterning systems in which extrinsic signals and intrinsic timers are integrated.

Morphogenesis of the amphibian limb blastema: The relationship between pattern and form

Development ◽  
1984 ◽  
Vol 79 (1) ◽  
pp. 165-181
Author(s):  
Nigel Holder ◽  
Susan Reynolds
Keyword(s):  
Pattern Formation ◽  
Vitamin A ◽  
Short Range ◽  
Range Cell ◽  
Limb Pattern ◽  
The Relationship ◽  
Pattern Regulation ◽  
Thigh Region ◽  
Short Arc ◽  
Number Of Cells

A relationship between pattern formation and field shape is established following the formation of rounded blastemas on lower arm limb stumps after treatment with vitamin A. Pattern formation is not affected by alteration in blastemal shape caused by removal of the dermis from the thigh region of the leg. We conclude, therefore, that blastemal shape does not play a causal role in establishing limb pattern. Data relating the number of cells present between the cardinal axial poles of blastemas and the size of blastemas is discussed in terms of short arc intercalation and short range cell—cell interactions during pattern regulation.

Patterns of cell division, cell death and chondrogenesis in cultured aggregates of normal and talpid3 mutant chick limb mesenchyme cells

Development ◽  
1972 ◽  
Vol 27 (1) ◽  
pp. 245-260
Author(s):  
D. A. Ede ◽  
O. P. Flint
Keyword(s):  
Cell Death ◽  
Cell Division ◽  
Limb Bud ◽  
Intercellular Matrix ◽  
Blue Stain ◽  
Special Pattern ◽  
Mesenchyme Cells ◽  
Division Cell ◽  
Made In

Aggregates were prepared from dissociated mesenchyme cells obtained from normal and talpid mutant chick limb buds at stage 26 and were maintained for 4 days in culture. They were shown by autoradiographic techniques to consist initially of populations of unifoimly dedifferentiated cells within which chondrogenesis was initiated between 1 and 2 days, leading to the formation of areas of precartilage in the interior of the aggregates. Measurements of cell population density, cell death and cell division were made in precartilage and non-cartilage regions on sections prepared from normal and mutant aggregates fixed at 1-day intervals and were related to the pattern of chondrogenesis. Non-cartilage areas consisted of cells surrounding the precartilage areas and extended to the surface of the aggregate; these cells showed no special pattern or histochemical reaction. Precartilage areas consisted of one or more “;condensations”, comprising cells arranged in concentric rings around a central cell or group of cells, characterized by uptake of [35S]sulphate and taking up alcian blue stain in the intercellular matrix. Chondrogenesis was initiated al the condensation foci and spread centrifugally. Condensations were arranged in a simple pattern, roughly equidistantly from each other and never at the surface of the aggregate. The shape and arrangement of the cells comprising them suggested that they were formed by a process of aggregation towards the condensation foci. The relation of these observations to events in the intact limb bud developing in vivo is discussed.

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