Production of congenital limb defects with retinoic acid: Phenomenological evidence of progressive differentiation during limb morphogenesis

1980 ◽  
Vol 161 (1) ◽  
pp. 105-113 ◽  
Author(s):  
T. E. Kwasigroch ◽  
D. M. Kochhar
Keyword(s):  
Retinoic Acid ◽  
Limb Defects ◽  
Limb Morphogenesis ◽  
Congenital Limb

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.

Processes involved in retinoic acid production of small embryonic palatal shelves and limb defects

Teratology ◽  
1990 ◽  
Vol 41 (3) ◽  
pp. 299-310 ◽  
Author(s):  
B. D. Abbott ◽  
L. G. Hill ◽  
L. S. Birnbaum
Keyword(s):  
Retinoic Acid ◽  
Acid Production ◽  
Limb Defects

scholarly journals Regulation of Dlx5 and Dlx6 gene expression by p63 is involved in EEC and SHFM congenital limb defects

Development ◽  
2008 ◽  
Vol 135 (7) ◽  
pp. 1377-1388 ◽  
Author(s):  
N. Lo Iacono ◽  
S. Mantero ◽  
A. Chiarelli ◽  
E. Garcia ◽  
A. A. Mills ◽  
...  
Keyword(s):  
Gene Expression ◽  
Limb Defects ◽  
Congenital Limb

Molecular approaches to vertebrate limb morphogenesis

Development ◽  
1989 ◽  
Vol 107 (Supplement) ◽  
pp. 121-131 ◽  
Author(s):  
Susan M. Smith ◽  
Kevin Pang ◽  
Olof Sundin ◽  
Sarah E. Wedden ◽  
Christina Thaller ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Cell Fate ◽  
Retinoic Acid Receptor ◽  
Active Form ◽  
Mirror Image ◽  
Biologically Active ◽  
Molecular Approaches ◽  
Limb Morphogenesis ◽  
Order Of Magnitude ◽  
Temporal Expression Pattern

It has long been proposed that concentration gradients of morphogens provide cues to specify cell fate in embryonic fields. Recent work in a variety of vertebrate systems give bona fide evidence that retinoic acid, the biologically active form of vitamin A, is a candidate for such a morphogen. In the developing chick wing, for example, locally applied retinoic acid triggers striking changes in the pattern along the anteroposterior axis. Instead of giving rise to a wing with the normal 234 digit pattern, wing buds treated with retinoic acid develop a 432234 mirror-image symmetrical digit pattern. For this review, we focus on three aspects of limb morphogenesis. (1) We summarize the experimental evidence supporting the notion that retinoic acid is a candidate morphogen. (2) Limb buds contain high levels of cellular retinoic-acid-binding protein (CRABP). Using order of magnitude calculations, we evaluate how the concentration of CRABP might affect the occupancy state of the retinoic acid receptor. (3) We discuss the spatio-temporal expression pattern of homeobox-containing genes in the developing limb and speculate about the possibility that retinoic acid influences the pattern of expression of homeobox genes.

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).

Prevalence and pattern of congenital limb defects in north of Iran

2015 ◽  
Vol 56 ◽  
pp. 30
Author(s):  
Mohammad Jafar Golalipour ◽  
Elaheh Golalipour ◽  
Nafiseh Kaviany ◽  
Aerzoo Mirfazeli ◽  
Naser Behnampour
Keyword(s):  
Limb Defects ◽  
North Of Iran ◽  
Congenital Limb
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