scholarly journals SHH propagates distal limb bud development by enhancing CYP26B1-mediated retinoic acid clearance via AER-FGF signalling

Development ◽  
2011 ◽  
Vol 138 (10) ◽  
pp. 1913-1923 ◽  
Author(s):  
S. Probst ◽  
C. Kraemer ◽  
P. Demougin ◽  
R. Sheth ◽  
G. R. Martin ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Limb Bud ◽  
Distal Limb ◽  
Bud Development ◽  
Acid Clearance ◽  
Fgf Signalling

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 Fibroblast growth factors (FGFs) prime the limb specific Shh enhancer for chromatin changes that balance histone acetylation mediated by E26 transformation-specific (ETS) factors

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Silvia Peluso ◽  
Adam Douglas ◽  
Alison Hill ◽  
Carlo De Angelis ◽  
Benjamin L Moore ◽  
...  
Keyword(s):  
Histone Acetylation ◽  
Limb Bud ◽  
Fibroblast Growth ◽  
Distal Limb ◽  
Inactive State ◽  
Dynamic Events ◽  
Active Enhancer ◽  
Mouse Limb ◽  
Fgf Signalling ◽  
Zone Of Polarizing Activity

Sonic hedgehog (Shh) expression in the limb bud organizing centre called the zone of polarizing activity is regulated by the ZRS enhancer. Here, we examine in mouse and in a mouse limb-derived cell line the dynamic events that activate and restrict the spatial activity of the ZRS. Fibroblast growth factor (FGF) signalling in the distal limb primes the ZRS at early embryonic stages maintaining a poised, but inactive state broadly across the distal limb mesenchyme. The E26 transformation-specific transcription factor, ETV4, which is induced by FGF signalling and acts as a repressor of ZRS activity, interacts with the histone deacetylase HDAC2 and ensures that the poised ZRS remains transcriptionally inactive. Conversely, GABPα, an activator of the ZRS, recruits p300, which is associated with histone acetylation (H3K27ac) indicative of an active enhancer. Hence, the primed but inactive state of the ZRS is induced by FGF signalling and in combination with balanced histone modification events establishes the restricted, active enhancer responsible for patterning the limb bud during development.

Retinoic acid and chick limb bud development

Development ◽  
1991 ◽  
Vol 113 (Supplement_1) ◽  
pp. 113-121 ◽  
Author(s):  
C. Tickle
Keyword(s):  
Retinoic Acid ◽  
Target Genes ◽  
Homeobox Gene ◽  
Experimental System ◽  
Shoulder Girdle ◽  
Limb Bud ◽  
Local Concentration ◽  
Anterior Position ◽  
Mesenchyme Cells ◽  
Vitamin A Derivative

The chick limb bud is a powerful experimental system in which to study pattern formation in vertebrate embryos. Exogenously applied retinoic acid, a vitamin A derivative, can bring about changes in pattern and, on several grounds, is a good candidate for an endogenous morphogen. As such, the local concentration of retinoic acid might provide cells with information about their position in relation to one axis of the limb. Alternatively, retinoic acid may be part of a more complex signalling system. Homeobox genes are possible target genes for regulation by retinoic acid in the limb. In particular, one homeobox gene, XlHbox 1 is expressed locally in the mesenchyme of vertebrate forelimbs and might code for an anterior position. When the pattern of the chick wing is changed by retinoic acid or by grafts of signalling tissue such that anterior cells now form posterior structures, the domain of XlHbox 1 expression expands rather than contracts. The expansion of XlHbox 1 expression correlates with shoulder girdle abnormalities. Retinoic acid application leads to visible changes in bud shape and this allows dissection of the way in which patterning is co-ordinated with morphogenesis. Results of recombination experiments and studies of changes in the apical ridge and proliferation in the mesenchyme suggest the following scheme: retinoic acid is involved in specification of position of mesenchyme cells; this specification determines their local interaction with the ridge that controls ridge morphology; the thickened apical ridge permits local proliferation in the underlying mesenchyme. The recent advances in molecular biology that permit analysis of the expression of various interesting genes in developing limbs hold out the promise that further investigation may soon allow a complete account of the patterning process in one part of the vertebrate embryo.

Vitamin A alters the internal viscosity of fragments of limb-bud mesenchyme

Development ◽  
1980 ◽  
Vol 59 (1) ◽  
pp. 325-339
Author(s):  
T. E. Kwasigroch ◽  
D. M. Kochhar
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Mesenchymal Cells ◽  
Limb Bud ◽  
Mouse Limb ◽  
Vitamin A Acid ◽  
Internal Viscosity ◽  
Fusion Experiments

Two techniques were used to examine the effect of vitamin A compounds (vitamin A acid = retinoic acid and vitamin A acetate) upon the relative strengths of adhesion among mouse limb-bud mesenchymal cells. Treatment with retinoic acid in vivo and with vitamin A acetate in vitro reduced the rate at which the fragments of mesenchyme rounded-up when cultured on a non-adhesive substratum, but these compounds did not alter the behavior of tissues tested in fragment-fusion experiments. These conflicting results indicate that the two tests measure different activities of cells and suggest that treatment with vitamin A alters the property(ies) of cells which regulate the internal viscosity of tissues.

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.

Etudes expérimentales sur le rôle des somites au cours des premiers stades du développement du membre antérieur chez l'embryon du Chélonien Emys orbicularis L.

Development ◽  
1974 ◽  
Vol 32 (2) ◽  
pp. 417-430
Author(s):  
Par J. Vasse
Keyword(s):  
Experimental Study ◽  
Developmental Stage ◽  
Limb Development ◽  
Limb Bud ◽  
Stages Of Development ◽  
Emys Orbicularis ◽  
Bud Development ◽  
Early Stages

Experimental study on the role of the somites during the early stages of development of the front limbs of the embryo of the chelonian Emys orbicularis L. Ablation of postotic somites 6–13 on one side in embryos of Emys orbicularis L. at the developmental stage when 20–23 somite pairs were present, led to arrest of forelimb-bud development in the somatopleure adjacent to the ablated somites on the operated side. Limb development in the somatopleure adjacent to intact somites on the operated side was unaffected, attaining the same stage as on the non-operated side. Ablation at later stages (25–33 somite pairs) did not prevent development of the limb adjacent to the ablated somites. When a part of the prospective somatopleure was injured, the remaining part formed a small limb-bud. When an obstacle was placed between the somatopleural mesoderm and the adjacent somite, development of the somatopleure stopped at this level. These results corroborate those obtained from previous studies in various reptilian embryos concerning the role of the ventral somite extensions as activators of proliferation in the somatopleural mesoderm. Injury to the ventral extension alone led to serious disturbances in the somatopleural mesoderm adjacent to this somite.

Inhibition and reversion of chondrogenesis by retinoic acid in rat limb bud cell cultures

1980 ◽  
Vol 189 (1) ◽  
pp. 25-33 ◽  
Author(s):  
Fran�oise Gallandre ◽  
Andreas Kistler ◽  
Brigitta Galli
Keyword(s):  
Retinoic Acid ◽  
Cell Cultures ◽  
Limb Bud
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