Kessel M
Max-Planck-Institut für biophysikalische Chemie, Göttingen, Germany.
Development. 1992 Jun;115(2):487-501. doi: 10.1242/dev.115.2.487.
In higher vertebrates, the formation of the body axis proceeds in a craniocaudal direction during gastrulation. Cell biological evidence suggests that mesoderm formation and specification of axial positions occur simultaneously. Exposure of gastrulating embryos to retinoic acid induces changes in axial patterns, e.g. anterior and posterior homeotic transformations of vertebrae. These morphological changes are accompanied by changes in the nonidentical, overlapping expression domains of Hox genes. In this report the influence of retinoic acid, administered at the end of and after gastrulation, on vertebral patterns is described. Anterior transformations and truncations affecting the caudal part of the vertebral column characterize animals exposed on day 8 and 9. 4 hours after retinoic acid administration on day 8 + 5 hours, Hox-1.8, Hox-1.9, and Hox-4.5 transcripts were not detected in their usual posterior expression domains, whereas transcripts of the anterior Hox-1.5 gene remained unaffected. 4 days after RA exposure on day 8 + 5 hours, Hox-1.8 expression was shifted posteriorly by an effectively low dose of RA, which induced the formation of supernumerary ribs. Hox-1.8 expression was limited to posterior, disorganized mesenchyme, bulging out neural tube, some intestinal loops and the hindlimb in truncated embryos exposed to a high dose of RA. A causal relation between the delayed activation of posterior Hox genes and anterior transformations or agenesis of vertebrae is discussed. On day 10.5 posterior transformations begin to occur in the cervical region, while later exposures again affect more caudal structures. The distribution of the transformations along the vertebral column indicates an influence of RA on migrating sclerotome cells before they are finally fixed in the cartilagenous vertebrae. The findings show that the mesodermal segments originally specified during gastrulation can be respecified in their second migratory phase, with effects spreading for a second time in a craniocaudal direction. The transformations are discussed with regard to a molecular specification of axial levels by Hox codes, defined as combinations of expressed Hox genes.
在高等脊椎动物中，原肠胚形成期间身体轴的形成是沿头尾方向进行的。细胞生物学证据表明，中胚层的形成和轴向位置的特化是同时发生的。将原肠胚期胚胎暴露于视黄酸会诱导轴向模式的变化，例如椎骨的前后同源异型转化。这些形态变化伴随着Hox基因不同的、重叠表达域的变化。在本报告中，描述了在原肠胚形成末期及之后给予视黄酸对椎骨模式的影响。影响脊柱尾部的前部转化和截断是第8天和第9天暴露的动物的特征。在第8天 + 5小时给予视黄酸4小时后，在其通常的后部表达域中未检测到Hox-1.8、Hox-1.9和Hox-4.5转录本，而前部Hox-1.5基因的转录本未受影响。在第8天 + 5小时暴露于视黄酸4天后，低剂量的视黄酸有效地使Hox-1.8表达向后移位，诱导了额外肋骨的形成。在暴露于高剂量视黄酸的截断胚胎中，Hox-1.8表达局限于后部、无序的间充质，突出于神经管、一些肠袢和后肢。讨论了后部Hox基因激活延迟与椎骨前部转化或发育不全之间的因果关系。在第10.5天，颈部开始出现后部转化，而后期暴露再次影响更靠尾端的结构。沿脊柱的转化分布表明视黄酸对迁移的生骨节细胞有影响，这些细胞最终会固定在软骨椎骨中。研究结果表明，原肠胚形成期间最初确定的中胚层节段在其第二次迁移阶段可以重新确定，其影响再次沿头尾方向扩散。根据Hox编码对轴向水平进行分子特化来讨论这些转化，Hox编码定义为表达的Hox基因的组合。
