The zone of polarizing activity: evidence for a role in normal chick limb morphogenesis

Development ◽  
1979 ◽  
Vol 50 (1) ◽  
pp. 217-233
Author(s):  
Dennis Summerbell
Keyword(s):  
Normal Development ◽  
Limb Bud ◽  
Concentration Profiles ◽  
Impermeable Barrier ◽  
Limb Morphogenesis ◽  
Zone Of Polarizing Activity

When an impermeable barrier is placed so as to divide the early chick limb-bud into anterior and posterior parts then development continues only on one side of the barrier. The detailed results are inconsistent with mosaic development. They can readily be explained by supposing that pattern is specified by the concentration of a diffusible morphogen controlled by the zone of polarizing activity. A simulation of appropriate concentration profiles is presented and its relevance to similar experiments published elsewhere is discussed. It seems probable that the zone of polarizing activity is active during normal development.

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.

Embryonic retinoic acid synthesis is required for forelimb growth and anteroposterior patterning in the mouse

Development ◽  
2002 ◽  
Vol 129 (15) ◽  
pp. 3563-3574 ◽  
Author(s):  
Karen Niederreither ◽  
Julien Vermot ◽  
Brigitte Schuhbaur ◽  
Pierre Chambon ◽  
Pascal Dollé
Keyword(s):  
Retinoic Acid ◽  
Sonic Hedgehog ◽  
Acid Synthesis ◽  
Limb Bud ◽  
Anteroposterior Patterning ◽  
Limb Morphogenesis ◽  
Functional Zone ◽  
Mutant Mouse Embryos ◽  
Bud Growth ◽  
Zone Of Polarizing Activity

Numerous studies, often performed on avian embryos, have implicated retinoic acid (RA) in the control of limb bud growth and patterning. Here we have investigated whether the lack of endogenous RA synthesis affects limb morphogenesis in mutant mouse embryos deficient for the retinaldehyde dehydrogenase 2 (Raldh2/Aldh1a2). These mutants, which have no detectable embryonic RA except in the developing retina, die at E9.5-E10 without any evidence of limb bud formation, but maternal RA supplementation through oral gavage from E7.5 can extend their survival. Such survivors exhibit highly reduced forelimb rudiments, but apparently normal hindlimbs. By providing RA within maternal food, we found both a stage- and dose-dependency for rescue of forelimb growth and patterning. Following RA supplementation from E7.5 to 8.5, mutant forelimbs are markedly hypoplastic and lack anteroposterior (AP) patterning, with a single medial cartilage and 1-2 digit rudiments. RA provided until E9.5 significantly rescues forelimb growth, but cannot restore normal AP patterning. Increasing the RA dose rescues the hypodactyly, but leads to lack of asymmetry of the digit pattern, with abnormally long first digit or symmetrical polydactyly. Mutant forelimb buds are characterized by lack of expression or abnormal distal distribution of Sonic hedgehog (Shh) transcripts, sometimes with highest expression anteriorly. Downregulation or ectopic anterior expression of Fgf4 is also seen. As a result, genes such as Bmp2 or Hoxd genes are expressed symmetrically along the AP axis of the forelimb buds, and/or later, of the autopod. We suggest that RA signaling cooperates with a posteriorly restricted factor such as dHand, to generate a functional zone of polarizing activity (ZPA).

Stimulation of division in mouse 3T3 cells by coculture with embryonic chick limb tissue

Development ◽  
1985 ◽  
Vol 86 (1) ◽  
pp. 219-226
Author(s):  
K. M. Bell ◽  
J. C. McLachlan
Keyword(s):  
Cell Division ◽  
Normal Development ◽  
Active Regions ◽  
Limb Bud ◽  
Embryonic Chick ◽  
3T3 Cells ◽  
Zone Of Polarizing Activity ◽  
Surgical Manipulation ◽  
Stimulation Of Division ◽  
Stimulation Of

Two regions of the chick limb bud — the apical ectodermal ridge and the zone of polarizing activity — have been shown to influence cell division and pattern formation during normal development and following surgical manipulation. In this study, using a simple coculture system, together with autoradiography, we have shown that these morphogenetically active regions of the limb bud can stimulate quiescent 3T3 cells to initiate DNA synthesis to a significantly greater degree than comparable but morphogenetically inactive regions of the limb bud.

Conservation of Pitx1 expression during amphibian limb morphogenesis

2006 ◽  
Vol 84 (2) ◽  
pp. 257-262 ◽  
Author(s):  
W Y Chang ◽  
F KhosrowShahian ◽  
M Wolanski ◽  
R Marshall ◽  
W McCormick ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Xenopus Laevis ◽  
Expression Patterns ◽  
Limb Bud ◽  
Eleutherodactylus Coqui ◽  
Limb Buds ◽  
Homeodomain Transcription Factor ◽  
Limb Morphogenesis ◽  
Pelvic Limb

In contrast to the pattern of limb emergence in mammals, chicks, and the newt N. viridescens, embryos such as Xenopus laevis and Eleutherodactylus coqui initiate pelvic limb buds before they develop pectoral ones. We studied the expression of Pitx1 in X. laevis and E. coqui to determine if this paired-like homeodomain transcription factor directs differentiation specifically of the hindlimb, or if it directs the second pair of limbs to form, namely the forelimbs. We also undertook to determine if embryonic expression patterns were recapitulated during the regeneration of an amputated limb bud. Pitx1 is expressed in hindlimbs in both X. laevis and E. coqui, and expression is similar in both developing and regenerating limb buds. Expression in hindlimbs is restricted to regions of proliferating mesenchyme.Key words: regeneration, Xenopus laevis, limb bud, Pitx1 protein, specification.

Mutations in mouse Aristaless-like4 cause Strong's luxoid polydactyly

Development ◽  
1998 ◽  
Vol 125 (14) ◽  
pp. 2711-2721 ◽  
Author(s):  
S. Qu ◽  
S.C. Tucker ◽  
J.S. Ehrlich ◽  
J.M. Levorse ◽  
L.A. Flaherty ◽  
...  
Keyword(s):  
Limb Development ◽  
Evolutionary Biology ◽  
Biochemical Characterization ◽  
Limb Bud ◽  
Critical Threshold ◽  
Homeodomain Protein ◽  
Loss Of Function ◽  
Posterior Aspect ◽  
Vertebrate Limb Development ◽  
Zone Of Polarizing Activity

Mutations that affect vertebrate limb development provide insight into pattern formation, evolutionary biology and human birth defects. Patterning of the limb axes depends on several interacting signaling centers; one of these, the zone of polarizing activity (ZPA), comprises a group of mesenchymal cells along the posterior aspect of the limb bud that express sonic hedgehog (Shh) and plays a key role in patterning the anterior-posterior (AP) axis. The mechanisms by which the ZPA and Shh expression are confined to the posterior aspect of the limb bud mesenchyme are not well understood. The polydactylous mouse mutant Strong's luxoid (lst) exhibits an ectopic anterior ZPA and expression of Shh that results in the formation of extra anterior digits. Here we describe a new chlorambucil-induced deletion allele, lstAlb, that uncovers the lst locus. Integration of the lst genetic and physical maps suggested the mouse Aristaless-like4 (Alx4) gene, which encodes a paired-type homeodomain protein that plays a role in limb patterning, as a strong molecular candidate for the Strong's luxoid gene. In genetic crosses, the three lst mutant alleles fail to complement an Alx4 gene-targeted allele. Molecular and biochemical characterization of the three lst alleles reveal mutations of the Alx4 gene that result in loss of function. Alx4 haploinsufficiency and the importance of strain-specific modifiers leading to polydactyly are indicative of a critical threshold requirement for Alx4 in a genetic program operating to restrict polarizing activity and Shh expression in the anterior mesenchyme of the limb bud, and suggest that mutations in Alx4 may also underlie human polydactyly.

A quantitative study of the growth and development of the ventral root in normal and experimental conditions

Development ◽  
1974 ◽  
Vol 32 (3) ◽  
pp. 819-833
Author(s):  
M. C. Prestige ◽  
Margaret A. Wilson
Keyword(s):  
Normal Development ◽  
Cell Number ◽  
Ventral Horn ◽  
Ventral Root ◽  
Limb Bud ◽  
Experimental Conditions ◽  
Collateral Sprouting ◽  
Cell Counts ◽  
Ventral Roots ◽  
Fibre Loss

1. The development of the ventral root (VR) in Xenopus has been studied by electron microscopy. Total fibre counts, and counts of classes of fibres were made from large photomontages of the whole of VR 9 at × 15000. 2. The total number of fibres in the root shows the same pattern of initial rise, peak, and subsequent decline that previous ventral horn (VH) cell counts had shown, The two curves overlay each other initially, but after the decline, there were apparently more cells than fibres. 3. Promyelin and myelin formation was seen at the time of the decline. There was no evidence that dying axons had started to myelinate. 4. In some animals the limb-bud was removed at the time of its first penetration by nerve fibres. The ventral roots developed normally for a week, but thereafter fibre loss was accentuated, advanced and more profound, so that after another week, no fibres were left. In these roots, no promyelin or myelin was formed. 5. In other animals, it was shown that there is no evidence for collateral sprouting in the ventral roots during normal development. 6. It is argued that the axons which die in normal development have already reached the limb-bud. 7. The correspondence between axon and cell number is discussed.

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.

scholarly journals Genetics and functions of the retinoic acid pathway, with special emphasis on the eye

2019 ◽  
Vol 13 (1) ◽  
Author(s):  
Brian Thompson ◽  
Nicholas Katsanis ◽  
Nicholas Apostolopoulos ◽  
David C. Thompson ◽  
Daniel W. Nebert ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Embryonic Development ◽  
Normal Development ◽  
Anterior Segment ◽  
Limb Bud ◽  
Optic Vesicle ◽  
Bud Development ◽  
Optic Cup ◽  
Multistep Process ◽  
Acid Pathway

AbstractRetinoic acid (RA) is a potent morphogen required for embryonic development. RA is formed in a multistep process from vitamin A (retinol); RA acts in a paracrine fashion to shape the developing eye and is essential for normal optic vesicle and anterior segment formation. Perturbation in RA-signaling can result in severe ocular developmental diseases—including microphthalmia, anophthalmia, and coloboma. RA-signaling is also essential for embryonic development and life, as indicated by the significant consequences of mutations in genes involved in RA-signaling. The requirement of RA-signaling for normal development is further supported by the manifestation of severe pathologies in animal models of RA deficiency—such as ventral lens rotation, failure of optic cup formation, and embryonic and postnatal lethality. In this review, we summarize RA-signaling, recent advances in our understanding of this pathway in eye development, and the requirement of RA-signaling for embryonic development (e.g., organogenesis and limb bud development) and life.

scholarly journals Ectopic Expression ofMsx-2in Posterior Limb Bud Mesoderm Impairs Limb Morphogenesis While InducingBMP-4Expression, Inhibiting Cell Proliferation, and Promoting Apoptosis

1998 ◽  
Vol 197 (1) ◽  
pp. 12-24 ◽  
Author(s):  
Deborah Ferrari ◽  
Alexander C. Lichtler ◽  
ZhongZong Pan ◽  
Caroline N. Dealy ◽  
William B. Upholt ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Ectopic Expression ◽  
Limb Bud ◽  
Posterior Limb ◽  
Limb Morphogenesis

The mesenchymal factor, FGF10, initiates and maintains the outgrowth of the chick limb bud through interaction with FGF8, an apical ectodermal factor

Development ◽  
1997 ◽  
Vol 124 (11) ◽  
pp. 2235-2244 ◽  
Author(s):  
H. Ohuchi ◽  
T. Nakagawa ◽  
A. Yamamoto ◽  
A. Araga ◽  
T. Ohata ◽  
...  
Keyword(s):  
Sonic Hedgehog ◽  
Limb Bud ◽  
Fibroblast Growth ◽  
Lateral Plate Mesoderm ◽  
Lateral Plate ◽  
Bud Formation ◽  
Limb Mesenchyme ◽  
Vertebrate Limb ◽  
Fgf10 Expression ◽  
Zone Of Polarizing Activity

Vertebrate limb formation has been known to be initiated by a factor(s) secreted from the lateral plate mesoderm. In this report, we provide evidence that a member of the fibroblast growth factor (FGF) family, FGF10, emanates from the prospective limb mesoderm to serve as an endogenous initiator for limb bud formation. Fgf10 expression in the prospective limb mesenchyme precedes Fgf8 expression in the nascent apical ectoderm. Ectopic application of FGF10 to the chick embryonic flank can induce Fgf8 expression in the adjacent ectoderm, resulting in the formation of an additional complete limb. Expression of Fgf10 persists in the mesenchyme of the established limb bud and appears to interact with Fgf8 in the apical ectoderm and Sonic hedgehog in the zone of polarizing activity. These results suggest that FGF10 is a key mesenchymal factor involved in the initial budding as well as the continuous outgrowth of vertebrate limbs.

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