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Pharmacological evidence for the role of RAR in axon guidance and embryonic development of a protostome species.
genesis ( IF 2.4 ) Pub Date : 2019-04-30 , DOI: 10.1002/dvg.23301
Alysha Johnson 1 , Eric de Hoog 1 , Michael Tolentino 1 , Tamara Nasser 1 , Gaynor E Spencer 1
Affiliation  

Retinoic acid (RA), the active metabolite of vitamin A, functions through nuclear receptors, one of which is the retinoic acid receptor (RAR). Though the RAR is essential for various aspects of vertebrate development, little is known about the role of RAR in nonchordate invertebrates. Here, we examined the potential role of an invertebrate RAR in mediating chemotropic effects of retinoic acid. The RAR of the protostome Lymnaea stagnalis is present in the growth cones of regenerating cultured motorneurons, and a synthetic RAR agonist (EC23), was able to mimic the effects of retinoic acid in inducing growth cone turning. We also examined the ability of the natural retinoids, all‐trans RA and 9‐cis RA, as well as the synthetic RAR agonists, to disrupt embryonic development in Lymnaea. Developmental defects included delays in embryo hatching, arrested eye, and shell development, as well as more severe abnormalities such as halted development. Developmental defects induced by some (but not all) synthetic RAR agonists were found to mimic those induced by addition of high concentrations of the natural retinoid isomers. These pharmacological data support a possible physiological role for the RAR in axon guidance and embryonic development of an invertebrate protostome species.

中文翻译:

RAR在轴突引导和原生动物物种胚胎发育中的作用的药理证据。

维甲酸A的活性代谢产物维甲酸(RA)通过核受体起作用,其中之一是维甲酸受体(RAR)。尽管RAR对于脊椎动物发育的各个方面都是必不可少的,但对于RAR在无脊椎无脊椎动物中的作用知之甚少。在这里,我们检查了无脊椎动物RAR在介导视黄酸的趋化作用中的潜在作用。原初定殖雄蕊的RAR存在于再生培养的运动神经元的生长锥中,合成的RAR激动剂(EC23)能够模拟视黄酸在诱导生长锥转向中的作用。我们还检查了天然类维生素A,全反式RA和9顺式的能力RA以及合成的RAR激动剂会破坏Lymnaea中的胚胎发育。发育缺陷包括胚胎孵化的延迟,眼睛的滞留和壳的发育,以及更严重的异常现象,例如发育停滞。发现由一些(但不是全部)合成RAR激动剂引起的发育缺陷可以模拟由于添加高浓度的天然类维生素A异构体而引起的发育缺陷。这些药理学数据支持RAR在无脊椎动物原生动物物种的轴突引导和胚胎发育中的可能生理作用。
更新日期:2019-04-30
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