The role of Wnt signals in the formation of posterior tissue in zebrafish

后脑后部和脊髓前部的形成受成纤维细胞生长因子（Fgf）和维甲酸（RA）信号以及Hox蛋白的控制。Fgf和RA信号是如何与Hox编码协同产生后脑后部和脊髓前部的，目前尚不清楚。我们证明，在斑马鱼胚胎中抑制尾端相关基因cdx1a和cdx4会导致后脑和前脊髓的后侧镜像复制，并且这种异位表达是细胞自主的。异位后神经组织中Fgf和RA信号的梯度与后脑和脊髓前区相反。我们在cdxla/4胚胎中进行了抑制Fgf和/或RA信号的实验。在缺乏Cdxla/4的胚胎中，这些组织的异位形成需要Fgf和RA信号。此外，在Cdxla/4下游起作用的hox后基因hoxb7a、hoxa9a或hoxb9a的表达抑制了这种功能丧失表型。我们发现，这些后Hox蛋白作为转录激活因子起作用，但抑制后后脑基因的异位表达。此外，hoxb1a或hoxb1b属于hox平行组1 (PG1)，参与后脑的形成，其错误表达可诱导前脑区域异位后后脑的形成，依赖于Fgf信号。cdx-hox编码改变神经组织对Fgfs和RA的反应能力。在Cdxla/4功能缺失和前Hoxs存在的情况下，神经组织能够对Fgf和RA信号做出后脑后向的反应。此外，Cdx蛋白通过调控后脑hox基因抑制后脑命运。

The formation of the posterior hindbrain and anterior spinal cord is controlled by fibroblast growth factor (Fgf) and retinoic acid (RA) signals, and by Hox proteins. It remains unresolved how the Fgf and RA signals cooperate with the Hox code to generate the posterior hindbrain and anterior spinal cord. We demonstrated that inhibiting the caudal-related genes cdx1a and cdx4 in zebrafish embryos causes a posterior, mirror-image duplication of the posterior hindbrain and anterior spinal cord, and this ectopic expression is cell-autonomous. The gradients of the Fgf and RA signals in the ectopic posterior neural tissue were opposite to those in the hindbrain and anterior spinal cord. We conducted experiments inhibiting Fgf and/or RA signaling in cdxla/4 morphant embryos. Fgf and RA signals were required for the ectopic formation of these tissues in embryos lacking Cdxla/4. In addition, expression of the posterior hox genes hoxb7a, hoxa9a, or hoxb9a, which function downstream of Cdxla/4, suppressed this loss-of-function phenotype. We showed that these posterior Hox proteins function as transcriptional activators, but repress the ectopic expression of posterior hindbrain genes. Furthermore, misexpression of hoxb1a or hoxb1b, which belong to hox paralog group 1 (PG1) and are involved in hindbrain formation, induced the formation of ectopic posterior hindbrain in the forebrain territory, Fgf signal-dependently. The cdx-hox code modifies tissue competence to respond to Fgfs and RA in neural tissue. In the absence of Cdxla/4 function and in the presence of the anterior Hoxs, neural tissue becomes competent to adopt the posterior hindbrain fate in response to Fgf and RA signals. Furthermore, Cdx proteins suppress the posterior hindbrain fate through regulation of the posterior hox genes.