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 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.

The structure of supernumerary limbs formed after 180° blastemal rotation in the newt Triturus cristatus

Development ◽  
1983 ◽  
Vol 74 (1) ◽  
pp. 143-158
Author(s):  
Spyros Papageorgiou ◽  
Nigel Holder
Keyword(s):  
Triturus Cristatus ◽  
Experimental Procedure ◽  
Skeletal Pattern ◽  
Supernumerary Limbs ◽  
Anterior Posterior ◽  
Anterior Posterior Axis

The structure of supernumerary limbs formed following 180° ipsilateral blastema rotations in the arm of the newt Triturus cristatus is analysed. Both the skeletal pattern and the muscle patterns are examined. As is the case after comparable experiments in the axolotl (see, for example, Maden & Mustafa, 1982) the extra limbs which form show a range of anatomies. Limbs symmetrical about the dorsal-ventral and anterior-posterior axis are reported as well as some limbs which were part symmetrical and part asymmetrical. It is clear that newts and axolotls appear to react in similar ways to this particular experimental procedure.

scholarly journals GLI transcriptional repression is inert prior to Hedgehog pathway activation

2021 ◽  
Author(s):  
Rachel K. Lex ◽  
Weiqiang Zhou ◽  
Zhicheng Ji ◽  
Kristin N. Falkenstein ◽  
Kaleigh E. Schuler ◽  
...  
Keyword(s):  
Transcriptional Repression ◽  
Limb Development ◽  
Target Genes ◽  
Hedgehog Pathway ◽  
Transcriptional Repressors ◽  
Posterior Limb ◽  
Gli Proteins ◽  
Pathway Activation ◽  
Hh Signaling ◽  
Anterior Posterior

In the absence of Hedgehog (HH) signaling, GLI proteins are post-translationally modified within cilia into transcriptional repressors that subsequently prevent sub-threshold activation of HH target genes. GLI repression is presumably important for preventing precocious expression of target genes before the onset of HH pathway activation, a presumption that underlies the pre-patterning model of anterior-posterior limb polarity. Here, we report that GLI3 repressor is abundant and binds to target genes in early limb development. However, contrary to expectations, GLI3 repression neither regulates the activity of GLI enhancers nor expression of HH target genes as it does after HH signaling has been established. Within the cilia, the transition to active GLI repression is accompanied by increases in axonemal GLI3 localization, possibly signifying altered GLI3 processing. Together, our results demonstrate that GLI3 repression does not prevent precocious activation of HH target genes, or have a pre-patterning role in regulating anterior-posterior limb polarity.

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.

Role of dHAND in the anterior-posterior polarization of the limb bud: implications for the Sonic hedgehog pathway

Development ◽  
2000 ◽  
Vol 127 (10) ◽  
pp. 2133-2142 ◽  
Author(s):  
M. Fernandez-Teran ◽  
M.E. Piedra ◽  
I.S. Kathiriya ◽  
D. Srivastava ◽  
J.C. Rodriguez-Rey ◽  
...  
Keyword(s):  
Sonic Hedgehog ◽  
Limb Development ◽  
Mirror Image ◽  
Limb Bud ◽  
Bhlh Transcription Factor ◽  
Cardiovascular Development ◽  
Anterior Border ◽  
Lateral Plate ◽  
Shh Pathway ◽  
Anterior Posterior

dHAND is a basic helix-loop-helix (bHLH) transcription factor essential for cardiovascular development. Here we analyze its pattern of expression and functional role during chick limb development. dHAND expression was observed in the lateral plate mesoderm prior to emergence of the limb buds. Coincident with limb initiation, expression of dHAND became restricted to the posterior half of the limb bud. Experimental procedures that caused mirror-image duplications of the limb resulted in mirror-image duplications of the pattern of dHAND expression along the anterior-posterior axis. Retroviral overexpression of dHAND in the limb bud produced preaxial polydactyly, corresponding to mild polarizing activity at the anterior border. At the molecular level, misexpression of dHAND caused ectopic activation of members of the Sonic hedgehog (Shh) pathway, including Gli and Patched, in the anterior limb bud. A subset of infected embryos displayed ectopic anterior activation of Shh. Other factors implicated in anterior-posterior polarization of the bud such as the most 5′ Hoxd genes and Bmp2 were also ectopically activated at the anterior border. Our results indicate a role for dHAND in the establishment of anterior-posterior polarization of the limb bud.

Why we have (only) five fingers per hand: hox genes and the evolution of paired limbs

Development ◽  
1992 ◽  
Vol 116 (2) ◽  
pp. 289-296 ◽  
Author(s):  
C.J. Tabin
Keyword(s):  
Limb Development ◽  
Hox Genes ◽  
Expression Patterns ◽  
Limb Bud ◽  
Developmental Constraint ◽  
Limb Morphogenesis ◽  
Different Types ◽  
Embryonic Limb ◽  
Limb Pattern ◽  
Anterior Posterior

Limb development has long been a model system for studying vertebrate pattern formation. The advent of molecular biology has allowed the identification of some of the key genes that regulate limb morphogenesis. One important class of such genes are the homeobox-containing, or Hox genes. Understanding of the roles these genes play in development additionally provides insights into the evolution of limb pattern. Hox gene expression patterns divide the embryonic limb bud into five sectors along the anterior/posterior axis. The expression of specific Hox genes in each domain specifies the developmental fate of that region. Because there are only five distinct Hox-encoded domains across the limb bud there is a developmental constraint prohibiting the evolution of more than five different types of digits. The expression patterns of Hox genes in modern embryonic limb buds also gives clues to the shape of the ancestral fin field from which the limb evolved, hence elucidating the evolution of the tetrapod limb.

Experiments on developing limb buds of the axolotl Ambystoma mexicanum

Development ◽  
1980 ◽  
Vol 57 (1) ◽  
pp. 177-187
Author(s):  
M. Maden ◽  
B. C. Goodwin
Keyword(s):  
Limb Development ◽  
Ambystoma Mexicanum ◽  
Limb Bud ◽  
Limb Buds ◽  
Vertebrate Limb ◽  
Two Systems ◽  
Vertebrate Limb Development ◽  
Supernumerary Limbs

Various experiments were performed on the limb buds of axolotls to compare the behaviour of amphibian limbs with that previously reported for chick limbs. Following removalof the tip or whole limb bud, extensive powers of regulation were observed since complete limbs always formed. Similarly after distal to proximal grafts intercalary regulation occurred to produce perfect limbs and after proximal to distal grafts serial repetitionsresulted. Transplantation and rotation of limb buds to reverse either the dorso-ventral,antero-posterior or both axes resulted in the induction of supernumerary limbs in a large proportion of cases. Such regulatory behaviour of axolotl limb buds is in contrast to the mosaic nature of chick limbs and as a result, theories such as the progress-zone theory which have been formulated on the basis of data from chick limbs are not relevant togeneral principles of vertebrate limb development. Possible reasons for the diverse behaviour between the two systems are discussed.

Experiments on Anuran limb buds and their significance for principles of vertebrate limb development

Development ◽  
1981 ◽  
Vol 63 (1) ◽  
pp. 243-265
Author(s):  
M. Maden
Keyword(s):  
Limb Development ◽  
Rana Temporaria ◽  
Limb Bud ◽  
Limb Buds ◽  
Dorsoventral Axis ◽  
Vertebrate Limb ◽  
Vertebrate Limb Development ◽  
Supernumerary Limbs ◽  
Standard Set ◽  
And Inversion

A standard set of six experiments performed on the limb buds of two species of Anurans - Rana temporaria and Xenopus laevis -are described. The experiments are limb-bud amputation, distal to proximal shifts, proximal to distal shifts, inversion of the dorsoventral axis inversion of the anteroposterior axis and inversion of both axes. The results are compared to those previously reported for Urodeles and chicks to determine whether any principles of vertebrate limb development can be formulated. It appears that the proximodistal axis becomes increasingly mosaic from the Urodeles through Anurans to chicks. In the transverse axes however, there is much more uniformity of behaviour in the production of supernumerary limbs. The relation between the type of limb development (regulative or mosaic) and the subsequent regenerative powers of the adult limb is discussed.

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