Exogenous retinoic acid induces digit reduction in opossums (Monodelphis domestica) by disrupting cell death and proliferation, and apical ectodermal ridge and zone of polarizing activity function

2015 ◽  
Vol 103 (3) ◽  
pp. 225-234 ◽  
Author(s):  
Anna C. Molineaux ◽  
Jennifer A. Maier ◽  
Teresa Schecker ◽  
Karen E. Sears
Keyword(s):  
Cell Death ◽  
Retinoic Acid ◽  
Apical Ectodermal Ridge ◽  
Monodelphis Domestica ◽  
Zone Of Polarizing Activity

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.

Retinoic acid regulates programmed cell death through BMP signalling

10.1038/10098 ◽  
1999 ◽  
Vol 1 (2) ◽  
pp. 125-126 ◽  
Author(s):  
J. Rodriguez-Leon ◽  
R. Merino ◽  
D. Macias ◽  
Y. Gañan ◽  
E. Santesteban ◽  
...  
Keyword(s):  
Cell Death ◽  
Retinoic Acid ◽  
Programmed Cell Death ◽  
Bmp Signalling

Retinoic acid application to chick wing buds leads to a dose-dependent reorganization of the apical ectodermal ridge that is mediated by the mesenchyme

Development ◽  
1989 ◽  
Vol 106 (4) ◽  
pp. 691-705 ◽  
Author(s):  
C. Tickle ◽  
A. Crawley ◽  
J. Farrar
Keyword(s):  
Retinoic Acid ◽  
Gap Junctions ◽  
Time Course ◽  
Apical Ectodermal Ridge ◽  
Threshold Response ◽  
Epithelial Morphology ◽  
Early Effects ◽  
High Doses ◽  
Columnar Cells ◽  
Dose Dependent

Local application of retinoic acid to wing buds of chick embryos leads to dose- and position-dependent changes in the pattern of cellular differentiation. Early effects of retinoid treatment on the apical ectodermal ridge coordinate pattern changes and morphogenesis. The length of the apical ridge increases when additional digits will form but decreases when digits are lost. These changes in length can be understood in terms of a threshold response to the local retinoid concentration that results in either disappearance or maintenance of the ridge (Lee & Tickle, J. Embryol. exp. Morph. 90, 139–169 (1985)). Here, we have analysed the mechanisms involved in ridge disappearance by locally applying retinoic acid to the apex of stage 20 chick wing buds. With this treatment regime, low doses give duplicated digit patterns and higher doses truncations. The height of the apical ridge is progressively reduced with increasing doses of retinoid and the time course of ridge flattening indicates that the height of the ridge is correlated with bud outgrowth. With high doses of retinoic acid, the typical ridge, a pseudostratified epithelium in which the columnar cells are tightly packed, disappears and the epithelium at the tip of the bud consists of loosely packed cuboidal cells. Shortly after treatment, there is a decrease in the number of gap junctions between ridge cells. This early change in cell contacts suggests that gap junctions may be involved in maintaining epithelial morphology. When treated epithelium is recombined with untreated mesenchyme, an apical ridge is reestablished and distal structures can be generated. In contrast, when treated mesenchyme is recombined with the epithelium from normal buds, only proximal structures are formed. Therefore, retinoids can lead to a reorganization of the apical ectodermal ridge which is mediated and maintained by the mesenchyme.

scholarly journals Constitutive Expression of the Promyelocytic Leukemia–Associated Oncogene PML-RARα in TF1 Cells: Isoform-Specific and Retinoic Acid–Dependent Effects on Growth, bcl-2 Expression, and Apoptosis

Blood ◽  
1998 ◽  
Vol 91 (9) ◽  
pp. 3347-3356 ◽  
Author(s):  
James L. Slack ◽  
Min Yu
Keyword(s):  
Cell Death ◽  
Retinoic Acid ◽  
Constitutive Expression ◽  
Promyelocytic Leukemia ◽  
Gm Csf ◽  
Functional Differences ◽  
All Trans Retinoic Acid ◽  
Erythroleukemia Cell ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony

Two major isoforms of PML-RARα are associated with (15;17)-positive acute promyelocytic leukemia (APL); however, functional differences between these isoforms have been difficult to define, and the molecular mechanism by which each isoform contributes to the pathogenesis of APL is not fully understood. To address these issues, the ‘short’ (S) and ‘long’ (L) isoforms of PML-RARα were constitutively expressed in the factor-dependent human erythroleukemia cell line, TF1. Expression of the L, but not the S, isoform inhibited growth of these cells in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF). In the absence of GM-CSF, the S isoform partially protected against apoptosis, while the L isoform accelerated cell death. Treatment with all-trans retinoic acid (ATRA) inhibited cell growth and caused apoptosis only in PML-RARα–expressing cells, and these effects of ATRA were more marked in cells expressing the L isoform. ATRA treatment also led to downregulation of bcl-2 and endogenous RARα in PML-RARα–expressing cells, but had little effect on the level of exogenously expressed PML-RARα. We conclude that (1) subtle differences exist in the biologic activities of the L and S isoforms of PML-RARα, and (2) both isoforms are capable of transducing an ATRA-mediated signal that leads to downregulation of bcl-2 and induction of programmed cell death.

Reduction of the rate of outgrowth, cell density, and cell division following removal of the apical ectodermal ridge of the chick limb-bud

Development ◽  
1977 ◽  
Vol 40 (1) ◽  
pp. 1-21
Author(s):  
Dennis Summerbell
Keyword(s):  
Cell Proliferation ◽  
Cell Death ◽  
Cell Division ◽  
Cell Density ◽  
Apical Ectodermal Ridge ◽  
Limb Bud ◽  
Short Term ◽  
Density Dependent ◽  
Wing Bud

Removal of the apical ectodermal ridge causes a reduction in the rate of outgrowth of the wing-bud and the loss of distal parts. More specifically it causes a short-term increase in cell density and cell death and a decrease in the rate of cell proliferation. The evidence supports the hypothesis of density-dependent control of cell division and suggests that there may also be a mechanism regulating skeletal length at the time of differentiation. An informal model is presented to explain the observations.

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.

An optimized retinoic acid-inducible gene I agonist M8 induces immunogenic cell death markers in human cancer cells and dendritic cell activation

2019 ◽  
Vol 68 (9) ◽  
pp. 1479-1492 ◽  
Author(s):  
Luciano Castiello ◽  
Alessandra Zevini ◽  
Elisabetta Vulpis ◽  
Michela Muscolini ◽  
Matteo Ferrari ◽  
...  
Keyword(s):  
Cell Death ◽  
Retinoic Acid ◽  
Dendritic Cell ◽  
Cancer Cells ◽  
Cell Activation ◽  
Human Cancer ◽  
Immunogenic Cell Death ◽  
Dendritic Cell Activation ◽  
Human Cancer Cells ◽  
Inducible Gene
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