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

点击翻译按钮获取中文摘要

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.