Control of pattern formation in urodele limb ontogeny: a review and a hypothesis

Development ◽  
1982 ◽  
Vol 69 (1) ◽  
pp. 7-36
Author(s):  
David L. Stocum ◽  
John F. Fallon

From a review of the literature, the hypothesis is advanced that the forelimb region of the urodele embryoacquires its transverse axial polarity and pattern by the action of posterior and dorsal polarizing regions. The anterior-posterior and dorsal-ventral axes are determined simultaneously and their determination is a prerequisite for proximal-distal outgrowth. Outgrowth of the limb bud is accompanied by the generation, between proximal and distal boundaries, of a set of positional values specifying proximal-distal axial polarity and pattern. The proximal boundary is the initial positional value carried by the cells of the limb area. The distal boundary is imposed upon the outermost layer of limb disc cells by the overlying ectoderm.

Development ◽  
1986 ◽  
Vol 94 (1) ◽  
pp. 267-275
Author(s):  
C. P. Cottrill ◽  
Paul T. Sharpe ◽  
Lewis Wolpert

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.


Development ◽  
1999 ◽  
Vol 126 (21) ◽  
pp. 4729-4736
Author(s):  
L. Lettice ◽  
J. Hecksher-Sorensen ◽  
R.E. Hill

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.


Development ◽  
1974 ◽  
Vol 32 (3) ◽  
pp. 651-660
Author(s):  
Dennis Summerbell

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.


Development ◽  
1982 ◽  
Vol 70 (1) ◽  
pp. 197-213
Author(s):  
M. Maden ◽  
K. Mustafa

An extensive series of skin grafting operations has been performed to investigate axial organization in the regenerating axolotl limb. Semicircular cuffs of skin from either anterior, posterior, dorsal or ventral surfaces were exchanged between right and left limbs thereby creating limbs with double anterior, double posterior, double dorsal or double ventral skin, all with normal internal tissues. Both fore and hindlimbs were used at both upper and lower limb levels. Following amputation through the grafted region the resulting regenerates were analysed both by whole-mount cartilage staining to observe the pattern of digits and by serial sectioning to observe the pattern of muscles. There were clear asymmetries in ability to produce duplications - posterior to anterior grafts resulted in a consistently high frequency of digital duplications, whereas anterior to posterior grafts produced very few. Similarly, dorsal to ventral grafts resulted in a good frequency of muscle duplications, whereas ventral to dorsal grafts did not. Such asymmetrical behaviour is not predicted by most models involving local cell:cell interactions and the significance of the results for theories of pattern formation is discussed.


Development ◽  
1974 ◽  
Vol 32 (1) ◽  
pp. 227-237
Author(s):  
Dennis Summerbell

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.


Development ◽  
2020 ◽  
Vol 147 (19) ◽  
pp. dev180042
Author(s):  
Hirotaka Tao ◽  
Jean-Philippe Lambert ◽  
Theodora M. Yung ◽  
Min Zhu ◽  
Noah A. Hahn ◽  
...  

ABSTRACTPattern formation is influenced by transcriptional regulation as well as by morphogenetic mechanisms that shape organ primordia, although factors that link these processes remain under-appreciated. Here we show that, apart from their established transcriptional roles in pattern formation, IRX3/5 help to shape the limb bud primordium by promoting the separation and intercalation of dividing mesodermal cells. Surprisingly, IRX3/5 are required for appropriate cell cycle progression and chromatid segregation during mitosis, possibly in a nontranscriptional manner. IRX3/5 associate with, promote the abundance of, and share overlapping functions with co-regulators of cell division such as the cohesin subunits SMC1, SMC3, NIPBL and CUX1. The findings imply that IRX3/5 coordinate early limb bud morphogenesis with skeletal pattern formation.


2020 ◽  
Vol 8 (4) ◽  
pp. 31
Author(s):  
Ines Desanlis ◽  
Rachel Paul ◽  
Marie Kmita

Limb patterning relies in large part on the function of the Hox family of developmental genes. While the differential expression of Hox genes shifts from the anterior–posterior (A–P) to the proximal–distal (P–D) axis around embryonic day 11 (E11), whether this shift coincides with a more global change of A–P to P–D patterning program remains unclear. By performing and analyzing the transcriptome of the developing limb bud from E10.5 to E12.5, at single-cell resolution, we have uncovered transcriptional trajectories that revealed a general switch from A–P to P–D genetic program between E10.5 and E11.5. Interestingly, all the transcriptional trajectories at E10.5 end with cells expressing either proximal or distal markers suggesting a progressive acquisition of P–D identity. Moreover, we identified three categories of genes expressed in the distal limb mesenchyme characterized by distinct temporal expression dynamics. Among these are Hoxa13 and Hoxd13 (Hox13 hereafter), which start to be expressed around E10.5, and importantly the binding of the HOX13 factors was observed within or in the neighborhood of several of the distal limb genes. Our data are consistent with previous evidence suggesting that the transition from the early/proximal to the late/distal transcriptome of the limb mesenchyme largely relies on HOX13 function. Based on these results and the evidence that HOX13 factors restrict Hoxa11 expression to the proximal limb, in progenitor cells of the zeugopod, we propose that HOX13 act as a key determinant of P–D patterning.


2003 ◽  
Vol 11 (03) ◽  
pp. 293-324 ◽  
Author(s):  
Anna Marciniak-Czochra

The aim of this paper is to show under which conditions a receptor-based model can produce and regulate patterns. Such model is applied to the pattern formation and regulation in a fresh water polyp, hydra. The model is based on the idea that both head and foot formation could be controlled by receptor-ligand binding. Positional value is determined by the density of bound receptors. The model is defined in the form of reaction-diffusion equations coupled with ordinary differential equations. The objective is to check what minimal processes are sufficient to produce patterns in the framework of a diffusion-driven (Turing-type) instability. Three-variable (describing the dynamics of ligands, free and bound receptors) and four-variable models (including also an enzyme cleaving the ligand) are analyzed and compared. The minimal three-variable model takes into consideration the density of free receptors, bound receptors and ligands. In such model patterns can evolve only if self-enhancement of free receptors, i.e., a positive feedback loop between the production of new free receptors and their present density, is assumed. The final pattern strongly depends on initial conditions. In the four-variable model a diffusion-driven instability occurs without the assumption that free receptors stimulate their own synthesis. It is shown that gradient in the density of bound receptors occurs if there is also a second diffusible substance, an enzyme, which degrades ligands. Numerical simulations are done to illustrate the analysis. The four-variable model is able to capture some results from cutting experiments and reflects de novo pattern formation from dissociated cells.


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