Conversion by retinoic acid of anterior cells into ZPA cells in the chick wing bud

Nature ◽  
1991 ◽  
Vol 350 (6313) ◽  
pp. 81-83 ◽  
Author(s):  
N. Wanek ◽  
D. M. Gardiner ◽  
K. Muneoka ◽  
S. V. Bryant
Keyword(s):  
Development ◽  
1996 ◽  
Vol 122 (5) ◽  
pp. 1385-1394 ◽  
Author(s):  
J.A. Helms ◽  
C.H. Kim ◽  
G. Eichele ◽  
C. Thaller

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.


Development ◽  
1994 ◽  
Vol 120 (11) ◽  
pp. 3267-3274 ◽  
Author(s):  
J. Helms ◽  
C. Thaller ◽  
G. Eichele

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.


Development ◽  
1994 ◽  
Vol 120 (1) ◽  
pp. 209-218 ◽  
Author(s):  
P.H. Francis ◽  
M.K. Richardson ◽  
P.M. Brickell ◽  
C. Tickle

We show here that bone morphogenetic protein 2 (BMP-2) is involved in patterning the developing chick limb. During early stages of limb development, mesenchymal expression of the Bmp-2 gene is restricted to the posterior part of the bud, in a domain that colocalizes with the polarizing region. The polarizing region is a group of cells at the posterior margin of the limb bud that can respecify the anteroposterior axis of the limb when grafted anteriorly and can activate expression of genes of the HoxD complex. We dissect possible roles of BMP-2 in the polarizing region signalling pathway by manipulating the developing wing bud. Retinoic acid application, which mimics the effects of polarizing region grafts, activates Bmp-2 gene expression in anterior cells. This shows that changes in anteroposterior pattern are correlated with changes in Bmp-2 expression. When polarizing region grafts are placed at the anterior margin of the wing bud, the grafts continue to express the Bmp-2 gene and also activate Bmp-2 expression in the adjacent anterior host mesenchyme. These data suggest that BMP-2 is part of the response pathway to the polarizing signal, rather than being the signal itself. In support of this, BMP-2 protein does not appear to have any detectable polarizing activity when applied to the wing bud. The pattern of Bmp-4 gene expression in the developing wing bud raises the possibility that BMP-2 and BMP-4 could act in concert. There is a close relationship, both temporal and spatial, between the activation of the Bmp-2 and Hoxd-13 genes in response to retinoic acid and polarizing region grafts, suggesting that expression of the two genes might be linked.


1994 ◽  
Vol 201 (4) ◽  
pp. 310-323 ◽  
Author(s):  
Douglas F. Paulsen ◽  
Wei-Dang Chen ◽  
David Okello ◽  
Benita Johnson

Development ◽  
1993 ◽  
Vol 118 (3) ◽  
pp. 957-965 ◽  
Author(s):  
C. Thaller ◽  
C. Hofmann ◽  
G. Eichele

The effects of retinoids are mediated by two types of receptors, the retinoic acid receptors (RARs) and the retinoid-X-receptors (RXRs). The physiological ligand of the RARs is all-trans-retinoic acid whereas RXRs have high affinity for 9-cis-retinoic acid, a naturally occurring retinoid isomer. RXRs are broadly expressed in embryonic and adult tissues, and they are capable of forming homodimers as well as heterodimers with RARs and other nuclear hormone receptors. The role of 9-cis-retinoic acid in regulating the activity of RXR homodimers and RXR-containing heterodimers is poorly understood in vivo. To begin to explore the function of 9-cis-retinoic acid in morphogenesis, we have examined the activity of this isomer in the chick wing. Using reverse transcriptase polymerase chain reaction analyses, we show that RXR gamma is expressed in stage 20 wing buds. Similar to all-trans-retinoic acid, the 9-cis-isomer induces pattern duplications when locally applied to chick wing buds, but the 9-cis isomer is about 25 times more potent than the all-trans form. Furthermore, applied all-trans-retinoic acid is converted to the 9-cis isomer in the wing bud. The ratio of 9-cis to all-trans-retinoic acid established in the tissue is approximately 1:25. This quantitative agreement between the degree of conversion and the 25-fold higher efficacy of the 9-cis isomer, raises the possibility that, at least in part, the effects of all-trans-retinoic acid on the wing pattern result from a conversion to the 9-cis isomer.(ABSTRACT TRUNCATED AT 250 WORDS)


2017 ◽  
Vol 246 (9) ◽  
pp. 682-690 ◽  
Author(s):  
Joseph Pickering ◽  
Neha Wali ◽  
Matthew Towers

2021 ◽  
Author(s):  
Holly Stainton ◽  
Matthew Towers

How development is timed between differently sized species is a fundamental question in biology. To address this problem, we compared wing development in the quail and the larger chick. We reveal that developmental timing is faster in the quail than in the chick, and is associated with pattern specification, proliferation, organiser duration, differentiation and apoptosis. However, developmental timing is independent of the growth rate, which is equivalent between both species, and therefore scales pattern to the size of the wing. We reveal that developmental timing can be either maintained or reset in interspecies tissue grafts, and we implicate retinoic acid as the resetting signal. Accordingly, retinoic acid can switch species developmental timing and rescale pattern, both between the quail and chick, and the chick and the larger turkey. We suggest that the scaling of pattern to wing bud size is achieved by the modulation of developmental timing against a comparable rate of growth.Summary- We show that developmental timing scales wing patterning


1990 ◽  
Vol 9 (10) ◽  
pp. 3093-3099 ◽  
Author(s):  
G. Oliver ◽  
E. M. De Robertis ◽  
L. Wolpert ◽  
C. Tickle
Keyword(s):  

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