Experimental Production of Congenital Malformations in Mammals by Metabolic Procedure

Kalter, Harold; Warkany, Josef

doi:10.1152/physrev.1959.39.1.69

Cited by 340 publications

(66 citation statements)

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“…Hale's work is recognized to be the first controlled and, as it turned out, successful attempt to produce congenital malformations in mammals and, in this respect, also represents the first demonstration that, in a mammalian embryo, environmental factors could influence developmental processes as effectively as hereditary forces (for review, see Kalter & Warkany, 1959). Following this pioneering work, the group of J Warkany (for review, see Wilson et al 1953) showed, half a century ago, that conceptuses of vitamin A-deficient (VAD) rat dams exhibit a large number of congenital abnormalities affecting the eyes, myocardium and aorticopulmonary septum, diaphragm, as well as respiratory and uro-genital systems.…”

Section: Retinoic Acid Receptors: Retinoic Acid-binding Proteinmentioning

confidence: 99%

A genetic dissection of the retinoid signalling pathway in the mouse

et al. 1999

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Section: Retinoic Acid Receptors: Retinoic Acid-binding Proteinmentioning

confidence: 99%

A genetic dissection of the retinoid signalling pathway in the mouse

et al. 1999

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“…Retinoic acid has been demonstrated to play a crucial role in the development of many tissues in the embryo, including the eye. Embryos that develop under conditions of vitamin A deficiency are often born with micropthalmia or anopthalmia (Kalter and Warkany, 1959). In zebrafish, RA activity is important for formation of the ventral eye (Hyatt et al, 1996b;Marsh-Armstrong et al, 1994), and later in the patterning/ differentiation of photoreceptors (Hyatt and Dowling, 1997;Hyatt et al, 1996a).…”

Section: Introductionmentioning

confidence: 99%

Retinoic acid regulates the expression of dorsoventral topographic guidance molecules in the chick retina

et al. 2005

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Asymmetric expression of several genes in the early eye anlagen is required for the dorsoventral (DV) and anteroposterior (AP) patterning of the retina. Some of these early patterning genes play a role in determining the graded expression of molecules that are needed to form the retinotectal map. The polarized expression of retinoic acid synthesizing and degrading enzymes along the DV axis in the retina leads to several zones of varied retinoic acid (RA)activity. This is suggestive of RA playing a role in DV patterning of the retina. A dominant-negative form of the retinoic acid receptor α(DNhRARα) was expressed in the chick retina to block RA activity. RA signaling was found to play a role in regulating the expression of EphB2,EphB3 and ephrin B2, three molecules whose graded expression in the retina along the DV axis is important for establishing the correct retinotectal map. Blocking RA signaling by misexpression of a RA degrading enzyme, Cyp26A1 recapitulated some but not all the effects of DNhRARα. It also was found that Vax, a ventrally expressed transcription factor that regulates the expression of the EphB and ephrin B molecules, functions upstream of, or in parallel to, RA. Expression of DNhRARα led to increased levels of RA-synthesizing enzymes and loss of RA-degrading enzymes. Activation of such compensatory mechanisms when RA activity is blocked suggests that RA homeostasis is very strictly regulated in the retina.

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“…Without this supply of RA, for example under conditions of maternal dietary deprivation (Kalter and Warkany, 1959;Heine et al, 1985;Dersch and Zile, 1993;Maden et al, 1996;Gale et al, 1999;Maden et al, 2000) or a null mutation in one of the enzymes that synthesizes RA (Niederreither et al, 1999), a battery of congenital defects result. Paradoxically, flooding this carefully regulated system by administering excess RA is also teratogenic, with many of the defects similar to those generated by a lack of vitamin A.…”

Section: Introductionmentioning

confidence: 99%

Generating gradients of retinoic acid in the chick embryo: Cyp26C1 expression and a comparative analysis of the Cyp26 enzymes

Reijntjes

Gale

Maden

2004

Developmental Dynamics

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We have cloned a novel retinoic acid (RA) catabolizing enzyme, Cyp26C1, in the chick and describe here its distribution during early stages of chick embryogenesis. It is expressed from stage 4 in the presumptive anterior (cephalic) mesoderm, in a subset of cephalic neural crest cells, the ventral otic vesicle, mesenchyme adjacent to the otic vesicle, the branchial pouches and grooves, a part of the neural retina, and the anterior telencephalon, and shows a dynamic expression in the hindbrain rhombomeres and neuronal populations within them. By examining the distribution of Cyp26C1 in the RA-free quail embryo, we can determine which of these expression domains is dependent on RA, and it is only the rhombomeric sites that do not appear, suggesting a role for RA in this location. The most striking domain of Cyp26C1 distribution is in the anterior cephalic mesoderm, which is adjacent to the domain of Raldh2 in the trunk mesoderm, but separated from it by a gap dorsal to which the posterior hindbrain will develop. We suggest that a gradient of RA within the mesoderm generated by Raldh2 and catabolized by Cyp26C1 could be responsible for patterning the hindbrain. We have compared this distribution of Cyp26C1 with that of Cyp26A1 and Cyp26B1 in the chick and shown that they generally occupy nonoverlapping sites of expression in the embryo, and as a result, we suggest individual roles for each of the Cyp enzymes in the developing embryo.

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Experimental Production of Congenital Malformations in Mammals by Metabolic Procedure

Cited by 340 publications

References 0 publications

A genetic dissection of the retinoid signalling pathway in the mouse

A genetic dissection of the retinoid signalling pathway in the mouse

Retinoic acid regulates the expression of dorsoventral topographic guidance molecules in the chick retina

Generating gradients of retinoic acid in the chick embryo: Cyp26C1 expression and a comparative analysis of the Cyp26 enzymes

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