Retinoic acid embryonic development

The central cleavage of P-carotene 1 is most likely the major pathway by which mammals produce the required retinoids il), in particular, retinal 2, which is essential for vision and is subsequently oxidized to retinoic acid 3 and reduced to retinol 4. An alternative excentric cleavage of 1 has been reported involving scission of the double bond at C7-C8 producing P-8 -apocarotenal 5 (2a,2b) which is subsequently oxidized to 2 (Fig. 1) (2c). The significance of carotene metabolites such as 2, 3 and 4 to embryonic development and other vital processes such as skin and membrane protection is a major concern of medicinal chemistry. 

Vitamin A is a fat-soluble vitamin involved in critical biological functions, such as embryonic development, growth and vision. It has three primary forms retinol, retinal and retinoic acid. In addition, (3-carotene can be converted to some extent in the body into retinol and is therefore called provitamin A. The bioactivity of these vitamin A compounds varies considerably, ranging from 100% for all-trans retinol, 75% for 13-eis retinol and to just 17% for (3-carotene. All-trans retinol is the major form of vitamin A in milk fat, with values ranging from 8.0 to 12.0 pg/g fat in samples of commercial butter. In contrast, 13-cA retinol is present at a very low... 

Maden M (2000) The role of retinoic acid in embryonic and post-embryonic development. Proceedings of the Nutrition Society 59, 65-73. 

Vitamin A is a fat-soluble vitamin. Chemically it is identical with the alcohol retinol, whereas the corresponding vitamin A aldehyd is retinal and the acid derivative of vitamin A is retinoic acid. A sufficient supply of vitamin A is required for embryonic growth and differentiation, for reproduction, including spermatogenesis, oogenesis and placental development and for vision in the developping and the adult organism. 

Colleoni S, Galli C, Caspar JA, Meganathan K, Jagtap S, Hescheler J, Sachinidis A, Lazzari G (2011) Development of a neural teratogenicity test based on human embryonic stem cells response to retinoic acid exposure. Toxicol Sci 124 370-377... 

Niederreither, K., Subbarayan, V., Dolle, P., Chambon, P. 1999. Embryonic retinoic acid synthesis is essential for early mouse post-implantation development. Nature Gen. 21, 444-448. 

Colbert, M.C., Linney, E., LaMantia, A.S. 1993. Local sources of retinoic acid coincide with retinoid-mediated transgene activity during embryonic development. Proc. Natl. Acad. Sci. USA 90, 6572-6576. 

Mendelsohn, C., Larkin, S., Mark, M., LeMeur, M., Clifford, J., Zelent, A., Chambon, P. 1994. RAR beta isoforms distinct transcriptional control by retinoic acid and specific spatial patterns of promoter activity during mouse embryonic development. Mech. Dev. 45, 227-241. 

Wendling, O., Ghyselinck, N.B., Chambon, P., Mark, M. 2001. Roles of retinoic acid receptors in early embryonic morphogenesis and hindbrain patterning. Development 128, 2031-2038. 

Vitamin A is a fat soluble vitamin derived from carotene. The alcohol form of vitamin A, retinol, is the storage form in the body. The aldehyde form, retinal, has a role in vision. The acid form, retinoic acid, functions in embryonic development. Vitamin A acts to some extent in the body as an antioxidant, protecting against oxidative damage. 

Most hormones interacting with intracellular receptors exert their effects by controlling rates of transcription of specific genes. In this case, the hormone binds to a receptor and the complex migrates to the nucleus, where it interacts with specific DNA sites. Hormones in this class include steroids, thyroid hormones (see here), and the hormonal forms of vitamin D. In addition, retinoids, derived from retinoic acid (related to vitamin A), exert regulatory effects in embryonic development through interactions with intracellular receptors. 

Rowe, A., Richman, J.M. Brickell, P.M. (1991). Retinoic acid treatment alters the distribution of retinoic acid receptor- transcripts in the embryonic chick face. Development, 111, 1007-16. 

General metabolic significance. (1) Somatic functions growth, development, and differentiation of epithelial and bone tissue (retinol, retinal, retinoic acid). (2) Reproduction spermatogenesis, development of the placenta, embryonic growth (retinol, retinal). (3) Visual process 11-cis-retinaldehyde is a prosthetic group of the visual pigments. 

Klug S, Creech-Kraft J, Wildi E, Merker H-J, Persaud TVN, Nau H, Neubert, D. (1989) Influence of 13-cis and all-trans retinoic acid on rat embryonic development in vitro correlation with isomerisation and drug transfer to the embryo. Arch Toxicol 63 185-192. 

In contrast to the other P450 family 26 P450s, P450 26C1 appears to be expressed mainly dirr-ing embryonic development, at least in animal models [2509]. Sites of expression include hindbrain, inner ear, first bronchial arch, tooth buds, and eqttatorial retina (of mice) [2533, 2534] However, low levels (of mRNA) can be detected in adult adrenal gland, lung, spleen, testis, and brain [2509, 2535]. Expression is also seen in keratinocyte cell lines treated with 9-cis- or all-irans-retinoic acid [2509]. 

Engberg, N., M. Kahn, D. R. Petersen, M. Hansson, and P. Serup. 2010. Retinoic Acid Synthesis Promotes Development of Neural Progenitors from Mouse Embryonic Stem Cells by Suppressing Endogenous, Wnt-Dependent Nodal Signaling. Stem Cells 28, no 9 1498-509. 

Kam, R. K., Y. Deng, Y. Chen, and H. Zhao. 2012. Retinoic Acid Synthesis and Functions in Early Embryonic Development. Cell Biosci 2, no 1 11. 

Mark, M., N. B. Ghyselinck, and P. Chambon. 2009. Function of Retinoic Acid Receptors During Embryonic Development. Nucl Recept Signal 7 e002. 

Niederreither, K., V. Subbarayan, P. Dolle, and P. Chambon. 1999. Embryonic Retinoic Acid Synthesis Is Essential for Early Monse Post-Implantation Development. Nat Genet 21, no 4 444-48. 

SandeU, L. L., B. W. Sanderson, G. Moiseyev, et al. 2007. RdhlO Is Essential for Synthesis of Embryonic Retinoic Acid and Is Required for Limb, Craniofacial, and Organ Development Genes Dev 21, no 9 1113—24. 

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