The molecular regulators that determine the precise position of the vertebrate limb along the anterio-posterior axis have not been identified. One model suggests that a combination of hox genes in the lateral plate mesoderm (LPM) promotes formation of the limb field, however redundancy among duplicated paralogs has made this model difficult to confirm. In this study, we identify an optimal window during mid-gastrulation stages when transient mis-regulation of retinoic acid signaling or the caudal related transcription factor, Cdx4, both known regulators of hox genes, can alter the position of the pectoral fin field. We show that increased levels of either RA or Cdx4 during mid-gastrulation are sufficient to rostrally shift the position of the pectoral fin field at the expense of surrounding gene expression in the anterior lateral plate mesoderm (aLPM). Alternatively, embryos deficient for both Cdx4 and Cdx1a (Cdx-deficient) form pectoral fins that are shifted towards the posterior and reveal an additional effect on size of the pectoral fin buds. Prior to formation of the pectoral fin buds, the fin field in Cdx-deficient embryos is visibly expanded into the posterior LPM (pLPM) region at the expense of surrounding gene expression. The effects on gene expression immediately post-gastrulation and during somitogenesis support a model where RA and Cdx4 act in parallel to regulate the position of the pectoral fin. Our transient method is a potentially useful model for studying the mechanisms of limb positioning along the AP axis.

中文翻译：

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Cdx 转录因子和视黄酸在原肠胚形成过程中胸鳍区域的前后位置中起平行作用

确定脊椎动物肢体沿前后轴的精确位置的分子调节剂尚未确定。一个模型表明，侧板中胚层 (LPM) 中的 hox 基因组合促进了肢体区域的形成，但是重复的旁系同源物之间的冗余使该模型难以证实。在这项研究中，当视黄酸信号或尾相关转录因子 Cdx4（两种已知的 hox 基因调节剂）的瞬时错误调节可以改变胸鳍区域的位置时，我们确定了中期原肠胚形成阶段的最佳窗口。我们表明，在原肠胚形成中期增加的 RA 或 Cdx4 水平足以以前侧板中胚层 (aLPM) 中周围基因表达为代价来改变胸鳍区域的位置。或者，缺乏 Cdx4 和 Cdx1a（Cdx 缺陷）的胚胎形成胸鳍，这些胸鳍向后移动，并显示出对胸鳍芽大小的额外影响。在胸鳍芽形成之前，Cdx 缺陷胚胎中的鳍区明显扩展到后 LPM (pLPM) 区域，但会牺牲周围的基因表达。在原肠胚形成后和体节发生过程中对基因表达的影响支持了一个模型，其中 RA 和 Cdx4 平行作用以调节胸鳍的位置。