Pigs Born without Eye Balls

Hale, Fred

doi:10.1007/978-94-011-6621-8_21

Cited by 46 publications

(22 citation statements)

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“…The eye is one part of the embryo which is particularly sensitive to retinoid deprivation (for example, see Hale, 1933), and, it is another region which has a fascinating distribution of these enzymes. In the dorsal hemisphere an aldehyde dehydrogenase known as AHD-2 is specifically expressed (McCaffery et al 1991(McCaffery et al , 1992(McCaffery et al , 1993Godbout et al 1996), and in the ventral hemisphere there is an enzyme known as V-1 (McCaffery et al 1993).…”

Section: Retinoid-synthesizing Enzymes In the Embryo And Their Knockoutsmentioning

confidence: 99%

“…In embryos which develop under conditions of vitamin A deficiency a wide range of abnormalities have been described since the first observation of Hale (1933) of a litter of pigs, all of whom had anophthalmia. These abnormalities, seen in rats, rabbits, cattle, sheep and human subjects (Kalter & Warkany, 1959), include defects of the central nervous system (CNS; hydrocephalus and spina bifida), eye (anophthalmia and microphthalmia), face (harelip and cleft palate), dentition, ear (accessory ear and otosclerosis), limb, urogenital system (cryptorchidism, ectopic ovaries, pseudohermaphroditism and renal defects), lungs (hypoplasia) and heart (incomplete ventricular septation, spongy myocardium, aortic arch defects, aorticopulmonary septal defects and valvulus communis).…”

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confidence: 99%

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The role of retinoic acid in embryonic and post-embryonic development

Maden

2000

Proc. Nutr. Soc.

116

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Retinoic acid (RA) is the bioactive metabolite of vitamin A (retinol) which acts on cells to establish or change the pattern of gene activity. Retinol is converted to RA by the action of two types of enzyme, retinol dehydrogenases and retinal dehydrogenases. In the nucleus RA acts as a ligand to activate two families of transcription factors, the RA receptors (RAR) and the retinoid X receptors (RXR) which heterodimerize and bind to the upstream sequences of RA-responsive genes. Thus, in addition to the well-established experimental paradigm of depriving animals of vitamin A to determine the role of RA in embryonic and post-embryonic development, molecular biology has provided us with two additional methodologies: knockout the enzymes or the RAR and RXR in the mouse embryo. The distribution of the enzymes and receptors, and recent experiments to determine the endogenous distribution of RA in the embryo are described here, as well as the effects on the embryo of knocking out the enzymes and receptors. In addition, recent studies using the classical vitamin A-deprivation technique are described, as they have provided novel insights into the regions of the embryo which crucially require RA, and the gene pathways involved in their development. Finally, the post-embryonic or regenerating systems in which RA plays a part are described, i.e. the regenerating limb, lung regeneration, hair cell regeneration in the ear and spinal cord regeneration in the adult.

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Section: Retinoid-synthesizing Enzymes In the Embryo And Their Knockoutsmentioning

confidence: 99%

mentioning

confidence: 99%

The role of retinoic acid in embryonic and post-embryonic development

Maden

2000

Proc. Nutr. Soc.

116

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“…Vitamin A (retinol), which is indispensable for eye development (Hale, 1933;Warkany and Schraffenberger, 1946;Wilson et al, 1953), exerts its biological functions through its metabolite, retinoic acid (RA). Two families of nuclear receptors, rexinoid receptor (RAR)␣, ␤ and ␥ (binding all trans-and 9cis-RA), and RXR␣, ␤ and ␥ (binding 9cis-RA only), transduce the RA signal (Chambon, 1996).…”

Section: Introductionmentioning

confidence: 99%

Retinoic acid-dependent eye morphogenesis is orchestrated by neural crest cells

et al. 2005

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(2) the expression of Foxc1 and Pitx2, which play crucial roles in anterior eye segment development; and (3) the growth of the ventral retina. We additionally show that RALDH1 and RALDH3 are the only enzymes that are required for RA synthesis in the eye region from E10.5 to E13.5, and that patterning of the dorsoventral axis of the retina does not require RA. Research articleDevelopment 4790 role in DV patterning Dräger et al., 2001;Peters and Cepko, 2002;Sakai et al., 2004).RALDH2, whose genetic ablation kills embryos at E9.5 (Niederreither et al., 1999;Mic et al., 2002), is required between E8.5 and E9.5 for optic cup formation and for setting up the correct expression of RALDH3 at later stages in the forming eye (Mic et al., 2004). RALDH1-null mice are viable and do not exhibit ocular defects, even though they lack RAdependent activity in the dorsal retina and in the corresponding axonal projections at E16.5 (Fan et al., 2003). RALDH3-null mice, which die at birth from respiratory distress due to choanal atresia, display only discrete ocular malformations, namely a retrolenticular membrane and a mild shortening of the ventral retina (Dupé et al., 2003). Furthermore, neither RALDH1-null nor RALDH3-null mice exhibit an altered DV patterning of the retina (Fan et al., 2003; Dupé et al., 2003). These observations raised the question as to whether the loss of RALDH1 or RALDH3 could be functionally compensated by RALDH3 or RALDH1, respectively, or by other RALDH proteins expressed in the eye region. To gain further insight into the roles of RA signaling pathways in the developing eye, we have analyzed the ocular phenotype of mutant mice (1) lacking both RALDH1 and RALDH3, and (2) lacking RAR␤ and RAR␥ selectively in the NCC-derived periocular mesenchyme (POM). We demonstrate that RA produced in the neural retina, the retinal pigmented epithelium and the corneal ectoderm by RALDH1 and RALDH3 acts in a paracrine manner to selectively control the expression of several genes in POM cells, whereas it is dispensable for the DV patterning of the retina. Materials and methods MiceAll mice, with a mixed C57BL/6ϫ129/Sv (50:50) genetic background, were housed in an animal facility licensed by the French Ministry of Agriculture , and all animal experiments were supervised by N.B.G. , who is qualified for experimenting with mice, in compliance with the European legislation on care and use of laboratory animals. The breeding diet (D03) contained 25000 UI of vitamin A per kg (UAR, Villemoisson sur Orge, France) and was provided ad libitum. Heterozygous mice were mated overnight, and animals with a vaginal plug at noon of the next day were considered as embryonic day (E) 0.5. Mice bearing loxP-flanked (floxed) RAR␤ (Rarb +/L2) and RAR␥ (Rarg +/L2) genes (Chapellier et al., 2002a; Chapellier, 2002b), as well as the Rare-hsp68-lacZ (Rossant et al., 1991), R26R (Soriano, 1999) and Wnt1-Cre (Danielian et al., 1998) transgenic mice were genotyped as described. Note that mutant fetuses lacking both RALDH1 and RALDH3 (hereafter designa...

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“…Vitamin A-deficient (VAD) embryos have multiple developmental abnormalities, including neural, heart, pharyngeal, limb, kidney, and eye defects (Evans, 1928;Hale, 1933;Wilson et al, 1953;Thompson et al, 1964). Conversely, addition of RA is teratogenic (Satre and Kochhar, 1989).…”

Section: Introductionmentioning

confidence: 99%