Johnson Alysha, de Hoog Eric, Tolentino Michael, Nasser Tamara, Spencer Gaynor E
Department of Biological Sciences, Brock University, St. Catharines, Ontario, Canada.
Genesis. 2019 Jul;57(7-8):e23301. doi: 10.1002/dvg.23301. Epub 2019 Apr 30.
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.
视黄酸（RA）是维生素A的活性代谢产物，通过核受体发挥作用，其中之一是视黄酸受体（RAR）。尽管RAR对脊椎动物发育的各个方面都至关重要，但关于RAR在无脊椎动物中的作用却知之甚少。在此，我们研究了一种无脊椎动物RAR在介导视黄酸趋化作用中的潜在作用。原口动物椎实螺的RAR存在于再生培养运动神经元的生长锥中，一种合成的RAR激动剂（EC23）能够模拟视黄酸诱导生长锥转向的作用。我们还研究了天然类视黄醇全反式视黄酸和9-顺式视黄酸以及合成RAR激动剂破坏椎实螺胚胎发育的能力。发育缺陷包括胚胎孵化延迟、眼睛和贝壳发育停滞，以及更严重的异常，如发育停止。发现一些（但不是全部）合成RAR激动剂诱导的发育缺陷类似于添加高浓度天然类视黄醇异构体所诱导的缺陷。这些药理学数据支持RAR在无脊椎动物原口动物物种的轴突导向和胚胎发育中可能具有生理作用。
