Stratford T, Logan C, Zile M, Maden M
Developmental Biology Research Centre, Biomedical Sciences Division, King's College London, London, UK.
Mech Dev. 1999 Mar;81(1-2):115-25. doi: 10.1016/s0925-4773(98)00231-7.
We describe here how the early limb bud of the quail embryo develops in the absence of retinoids, including retinoic acid. Retinoid-deficient embryos develop to about stage 20/21, thus allowing patterns of early gene activity in the limb bud to be readily examined. Genes representing different aspects of limb polarity were analysed. Concerning the anteroposterior axis, Hoxb-8 was up-regulated and its border was shifted anteriorly whereas shh and the mesodermal expression of bmp-2 were down-regulated in the absence of retinoids. Concerning the apical ectodermal genes, fgf-4 was down-regulated whereas fgf-8 and the ectodermal domain of bmp-2 were unaffected. Genes involved in dorsoventral polarity were all disrupted. Wnt-7a, normally confined to the dorsal ectoderm, was ectopically expressed in the ventral ectoderm and the corresponding dorsal mesodermal gene Lmx-1 spread into the ventral mesoderm. En-1 was partially or completely absent from the ventral ectoderm. These dorsoventral patterns of expression resemble those seen in En-1 knockout mouse limb buds. Overall, the patterns of gene expression are also similar to the Japanese limbless mutant. These experiments demonstrate that the retinoid-deficient embryo is a valuable tool for dissecting pathways of gene activity in the limb bud and reveal for the first time a role for retinoic acid in the organisation of the dorsoventral axis.
我们在此描述鹌鹑胚胎的早期肢芽在缺乏类视黄醇（包括视黄酸）的情况下是如何发育的。缺乏类视黄醇的胚胎发育到约第20/21阶段，从而使得肢芽中早期基因活性模式易于被检测。分析了代表肢极性不同方面的基因。关于前后轴，在缺乏类视黄醇的情况下，Hoxb - 8上调，其边界向前移动，而shh和bmp - 2的中胚层表达下调。关于顶端外胚层基因，fgf - 4下调，而fgf - 8和bmp - 2的外胚层结构域未受影响。涉及背腹极性的基因均被破坏。通常局限于背侧外胚层的Wnt - 7a在腹侧外胚层异位表达，相应的背侧中胚层基因Lmx - 1扩散到腹侧中胚层。腹侧外胚层中En - 1部分或完全缺失。这些背腹表达模式类似于在En - 1基因敲除小鼠肢芽中看到的模式。总体而言，基因表达模式也与日本无肢突变体相似。这些实验表明，缺乏类视黄醇的胚胎是剖析肢芽中基因活性途径的有价值工具，并首次揭示了视黄酸在背腹轴组织中的作用。
