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

后脑和前脊髓的形成受成纤维细胞生长因子和维甲酸信号以及HOX蛋白的控制。目前尚不清楚成纤维细胞生长因子和类风湿因子信号如何与HOX编码一起产生后后脑和前脊髓。我们证明，在斑马鱼胚胎中抑制尾部相关基因cdx1a和cdx4会导致后后脑和前脊髓的镜像复制，并且这种异位表达是细胞自主的。在异位后神经组织中，成纤维细胞生长因子和类风湿因子的信号强度与后脑和脊髓前部的信号强度相反。我们在cdxla/4变异体胚胎中进行了抑制成纤维细胞生长因子和/或RA信号的实验。在缺乏CDx1a/4的胚胎中，这些组织的异位形成需要FGF和RA信号。此外，在CDx1a/4下游发挥作用的后部Hox基因hoxb7a、hoxa9a或hoxb9a的表达抑制了这种功能丧失的表型。我们发现，这些后脑HOX蛋白作为转录激活剂发挥作用，但抑制后脑基因的异位表达。此外，Hox paralog group 1(PG1)中参与后脑形成的hoxb1a或hoxb1b的错误表达诱导了前脑区异位后后脑的形成，这是成纤维细胞生长因子信号依赖的。CDX-HOX编码改变神经组织中组织对FGFs和RA的反应能力。在缺乏CDX1a/4功能的情况下，在前HOX存在的情况下，神经组织能够响应成纤维细胞生长因子和类风湿因子信号而采用后脑命运。此外，CDX蛋白通过对后脑HOX基因的调控抑制了后脑的命运。

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.