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• W2016184998 abstract "Abstract We have recently developed a range of synthetic retinoid analogues which include the compounds EC 23 and EC 19. They are stable on exposure to light and are predicted to be resistant to the normal metabolic processes involved in the inactivation of retinoids in vivo . Based on the position of the terminal carboxylic acid groups in the compounds we suggest that EC 23 is a structural analogue of all‐trans retinoic acid ( ATRA ), and EC 19 is an analogue of 13‐cis retinoic acid. Their effects on the differentiation of pluripotent stem cells has been previously described in vitro and are consistent with this hypothesis. We present herein the first description of the effects of these molecules in vivo . Retinoids were applied to the anterior limb buds of chicken embryos in ovo via ion‐exchange beads. We found that retinoid EC 23 produces effects on the wing digits similar to ATRA , but does so at two orders of magnitude lower concentration. When larger quantities of EC 23 are applied, a novel phenotype is obtained involving production of multiple digit 1s on the anterior limb. This corresponds to differential effects of ATRA and EC 23 on sonic hedgehog ( shh ) expression in the developing limb bud. With EC 23 application we also find digit 1 phenotypes similar to thumb duplications described in the clinical literature. EC 23 and ATRA are shown to have effects on the entire proximal–distal axis of the limb, including hitherto undescribed effects on the scapula. This includes suppression of expression of the scapula marker Pax1 . EC 23 also produces effects similar to those of ATRA on the developing face, producing reductions of the upper beak at concentrations two orders of magnitude lower than ATRA . In contrast, EC 19, which is structurally very similar to EC 23, has novel, less severe effects on the face and rarely alters limb development. EC 19 and ATRA are effective at similar concentrations. These results further demonstrate the ability of retinoids to influence embryonic development. Moreover, EC 23 represents a useful new tool to investigate developmental processes and probe the mechanisms underlying congenital abnormalities in vertebrates including man." @default.
• W2016184998 created "2016-06-24" @default.
• W2016184998 creator A5011748145 @default.
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• W2016184998 date "2013-12-04" @default.
• W2016184998 modified "2023-10-03" @default.
• W2016184998 title "Application of synthetic photostable retinoids induces novel limb and facial phenotypes during chick embryogenesis<i>in vivo</i>" @default.
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• W2016184998 doi "https://doi.org/10.1111/joa.12147" @default.

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