Induction of Normal Cardiovascular Development in the Vitamin A-Deprived Quail Embryo by Natural Retinoids

Dersch, Helen; Zile, Maija H.

doi:10.1006/dbio.1993.1318

Cited by 170 publications

(124 citation statements)

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“…These fetuses are more likely comparable to the nutritionally partially vitamin A-deprived rodent fetuses (Smith et al, 1998;White et al, 2000), i.e., the embryos became vitamin A depleted at a somewhat later time in embryogenesis and, clearly, certain early developmental events had proceeded in the presence of some vitamin A. The fetal VAD syndrome, as the term is currently used, encompasses many abnormalities with their origin linked to the time in development when RA function was lacking; a complete absence of vitamin A starting at fertilization encompasses a more severe phenotype and results in very early embryolethality as has been unequivocally demonstrated only in the VAD quail embryo model (Dersch and Zile, 1993;Zile, 2001). Taking advantage of the specificity of this avian VAD embryo model, we address the roles of individual retinoid receptors during early embryonic development by loss-of-function analysis by using the retinoid ligand knockout embryos, combined with in situ hybridization analysis and the use of AS to the retinoid receptor transcripts.…”

Section: Blocking Activity Of Rar␣2 Rar␥ and Rxr␣ Affects The Exprementioning

confidence: 99%

“…Earlier work has suggested an important role for vitamin A in cardiac inflow tract formation (Heine et al, 1985;Dersch and Zile, 1993;Kostetskii et al, 1999;Ghatpande et al, 2000). The presence of RA-generating enzymes in the heart-forming regions (Niederreither et al, 1997;Moss et al, 1998;Maden et al, 1998) also supports a role for RA in the heart morphogenesis, but there are no data regarding the specific functions of individual retinoid receptors in avian heart development (Kubalak and Sucov, 1999).…”

Section: Rar␣2 Has a Distinct Role In Cardiac Inflow Tract Morphogenesismentioning

confidence: 99%

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Function of RARγ and RARα2 at the initiation of retinoid signaling is essential for avian embryo survival and for distinct events in cardiac morphogenesis

Romeih

Cui

Michaille

et al. 2003

Developmental Dynamics

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Section: Blocking Activity Of Rar␣2 Rar␥ and Rxr␣ Affects The Exprementioning

confidence: 99%

Section: Rar␣2 Has a Distinct Role In Cardiac Inflow Tract Morphogenesismentioning

confidence: 99%

Function of RARγ and RARα2 at the initiation of retinoid signaling is essential for avian embryo survival and for distinct events in cardiac morphogenesis

Romeih

Cui

Michaille

et al. 2003

Developmental Dynamics

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“…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). An additional defect seen in chick and quail embryos is in the haematopoetic system, with the failure of the vitelline veins to form (Thompson et al 1969;Dersch & Zile, 1993).…”

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confidence: 99%

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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“…Normal and VAD quail eggs were generated using defined diets as described (Dersch and Zile, 1993). Quail eggs were incubated in a humidified egg chamber at 38°C to desired stages of development (Hamburger and Hamilton, 1951).…”

Section: Experimental Procedures Embryo Cultures and Explantsmentioning

confidence: 99%

“…Since RA must be provided in the diet or synthesized from dietary retinoid derivatives, this can be achieved in models of vitamin A deficiency (VAD). A particularly "tight" system with respect to complete loss of function was developed in the quail system (Dersch and Zile, 1993;Zile, 1999). The basis for a VAD model is the fact that an embryo must metabolize RA from maternal stores of Vitamin A.…”

Section: Introductionmentioning

confidence: 99%

Bmp2 and Gata4 function additively to rescue heart tube development in the absence of retinoids

Ghatpande

Brand

Zile

et al. 2006

Developmental Dynamics

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We used the vitamin A-deficient (VAD) quail model to investigate the retinoid-dependent mechanism that regulates heart tube development. We showed previously that decreased levels of Gata4 in cardiogenic mesoderm and endoderm correlate with the cardiomyopathy caused by VAD, but that this could be rescued by transplanting normal anterior endoderm. Bmp2 is a known cardiogenic factor that is expressed normally in lateral plate mesoderm and cardiac-associated pharyngeal endoderm. Here we show that (like Gata4) transcripts encoding Bmp2 and BMP-dependent signaling activity are decreased throughout the heartforming region of the VAD embryo. Addition of Bmp2 protein or forced expression of Gata4 in cultured VAD embryos leads to a partial rescue of the cardiomyopathy, and addition of both Bmp2 and Gata4 has an additive positive effect. Our data are consistent with a requirement for retinoid signaling to maintain expression of Bmp2, which regulates Gata4, and in addition acts with Gata4 to regulate genes important for normal morphogenesis of the primitive heart tube.

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Induction of Normal Cardiovascular Development in the Vitamin A-Deprived Quail Embryo by Natural Retinoids

Cited by 170 publications

References 0 publications

Function of RARγ and RARα2 at the initiation of retinoid signaling is essential for avian embryo survival and for distinct events in cardiac morphogenesis

Function of RARγ and RARα2 at the initiation of retinoid signaling is essential for avian embryo survival and for distinct events in cardiac morphogenesis

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

Bmp2 and Gata4 function additively to rescue heart tube development in the absence of retinoids

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