Cdx-Hox code controls competence for responding to Fgfs and retinoic acid in zebrafish neural tissue
Cdx-Hox code controls competence for responding to Fgfs and retinoic acid in zebrafish neural tissue
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DOI：
10.1242/dev.02660
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发表时间：
2006-12
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影响因子：
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通讯作者：
Takashi Shimizu;Y. Bae;M. Hibi
中科院分区：
文献类型：
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作者：
Takashi Shimizu;Y. Bae;M. Hibi
成纤维细胞生长因子 (Fgf) 和视黄酸 (RA) 信号控制后后脑的形成和前后模式。它们还参与胚胎其他区域的发育过程。因此，必须以上下文相关的方式控制对 Fgf 和 RA 信号的响应。抑制斑马鱼胚胎中尾部相关基因 cdx1a 和 cdx4 会导致通常在后脑和前脊髓中表达的基因异位表达，以及最后神经组织中后脑运动神经元和连合神经元的异位形成。组合标记分析表明 Cdx1a/4 缺陷胚胎中存在镜像重复，细胞移植分析进一步揭示 Cdx1a 和 Cdx4 在后神经组织中自主抑制后脑特异性基因表达细胞。 fgfs 和视黄醛脱氢酶 2 的表达表明，在 Cdx1a/4 缺陷胚胎中，与后脑区域相比，Fgf 和 RA 信号传导活动在后体重叠，并表现出相反的梯度。我们发现Fgf和RA信号是异位表达所必需的。后hox基因hoxb7a、hoxa9a或hoxb9a（其在Cdx1a/4下游发挥作用）或hoxa9a或hoxb9a的激活融合基因（VP16-hoxa9a、VP16-hoxb9a）的表达抑制了这种功能丧失表型。这些数据表明，Cdx 通过调节后 hox 基因来抑制后后脑命运。后Hox蛋白作为转录激活剂发挥作用，间接抑制后神经组织中后后脑基因的异位表达。我们的结果表明，Cdx-Hox 代码改变了组织对神经组织中 Fgfs 和 RA 的反应能力。
Fibroblast growth factor (Fgf) and retinoic acid (RA) signals control the formation and anteroposterior patterning of posterior hindbrain. They are also involved in development processes in other regions of the embryo. Therefore, responsiveness to Fgf and RA signals must be controlled in a context-dependent manner. Inhibiting the caudal-related genes cdx1a and cdx4 in zebrafish embryos caused ectopic expression of genes that are normally expressed in the posterior hindbrain and anterior spinal cord, and ectopic formation of the hindbrain motor and commissure neurons in the posteriormost neural tissue. Combinational marker analyses suggest mirror-image duplication in the Cdx1a/4-defective embryos, and cell transplantation analysis further revealed that Cdx1a and Cdx4 repress a posterior hindbrain-specific gene expression cell-autonomously in the posterior neural tissue. Expression of fgfs and retinaldehyde dehydrogenase 2 suggested that in the Cdx1a/4-defective embryos, the Fgf and RA signaling activities overlap in the posterior body and display opposing gradients, compared with those in the hindbrain region. We found that Fgf and RA signals were required for ectopic expression. Expression of the posterior hox genes hoxb7a, hoxa9a or hoxb9a, which function downstream of Cdx1a/4, or activator fusion genes of hoxa9a or hoxb9a (VP16-hoxa9a, VP16-hoxb9a) suppressed this loss-of-function phenotype. These data suggest that Cdx suppresses the posterior hindbrain fate through regulation of the posterior hox genes; the posterior Hox proteins function as transcriptional activators and indirectly repress the ectopic expression of the posterior hindbrain genes in the posterior neural tissue. Our results indicate that the Cdx-Hox code modifies tissue competence to respond to Fgfs and RA in neural tissue.