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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Spatiotemporal retinoid-X receptor activation detected in live vertebrate embryos
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Spatiotemporal retinoid-X receptor activation detected in live vertebrate embryos

机译：在活的脊椎动物胚胎中检测到时空类维生素A X受体激活

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Most studies on the nuclear retinoid-X receptor (RXR) have focused on its role as a heterodimeric partner but less about its own activation pattern during development and the distribution of potential endogenous ligands. The aim of this study is to visualize the distribution of activated RXRalpha in live transgenic Xenopus laevis embryos across a wide range of developmental stages. We adopted a nuclear receptor-Gal4 fusion/upstream activation sequence-based reporter system for our assay. Strong activation of the RXRa ligand-binding domain was observed in a segment of the spinal cord just posterior to the hindbrain. This activation is first detected in neurula stage embryos and persists up to swimming tadpole stages, after which activation strongly declines. Addition of exogenous ligands, such as 9-cis retinoic acid or all-trans retinoic acid, expands the activation of RXR throughout the spinal cord but not in the brain, whereas the RXR-specific ligand LG268 expanded the Gal4-RXR activation into the brain and olfactory epithelia. Treatment with the RAR-specific ligand 4-(E-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl) benzoic acid or thyroid hormone had no effect on Gal4-RXR activation, whereas these compounds significantly increased their corresponding Gal4/ receptor fusion proteins under similar conditions. Embryos expressing a Gal4-RXR fusion protein with a deletion in the ligand-dependent activation domain (AF2) show no reporter gene activation. The results shown in this paper reveal a specific activation pattern for Gal4-RXRalpha specifically in the developing spinal cord and suggest the existence of RXR ligand "hot-spots" in this region.
机译：关于核类视黄醇X受体（RXR）的大多数研究都集中于其作为异二聚体伴侣的作用，而很少涉及其自身在发育过程中和潜在内源性配体分布过程中的激活方式。这项研究的目的是可视化活化的RXRalpha在整个发展阶段的活的转基因非洲爪蟾胚胎中的分布。我们采用了基于核受体-Gal4融合/上游激活序列的报告系统进行检测。在后脑后部的脊髓节段中观察到RXRa配体结合结构域的强烈激活。这种激活首先在神经元阶段的胚胎中检测到，并一直持续到游泳的stages阶段，此后激活强烈下降。添加外源性配体（例如9-顺式视黄酸或全反式视黄酸）可扩展RXR在整个脊髓中的激活，但不在整个大脑中，而RXR特异性配体LG268可将Gal4-RXR激活扩展到大脑中。和嗅觉上皮。用RAR特异性配体4-（E-2-（5,6,7,8-四氢-5,5,8,8-四甲基-2-萘基）-1-丙烯基）苯甲酸或甲状腺激素进行治疗对Gal4-RXR活化没有影响，而这些化合物在相似条件下显着增加了其相应的Gal4 /受体融合蛋白。表达在配体依赖性激活域（AF2）中缺失的Gal4-RXR融合蛋白的胚胎未显示报告基因激活。本文显示的结果揭示了Gal4-RXRalpha在激活的脊髓中的特异性激活模式，并暗示了该区域存在RXR配体“热点”。

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