Department for Molecular Biomedical Research, Flanders Institute for Biotechnology VIB, B-9052 Ghent Belgium.
Proc Natl Acad Sci U S A. 2010 Sep 14;107(37):16160-5. doi: 10.1073/pnas.1007725107. Epub 2010 Aug 30.
The formation of primitive (embryonic) blood in vertebrates is mediated by spatio-temporally restricted signaling between different tissue layers. In Xenopus, in which primitive blood originates in the ventral blood island, this involves the secretion of bone morphogenetic protein (BMP) ligands by the ectoderm that signal to the underlying mesoderm during gastrulation. Using novel transgenic reporter lines, we report that the canonical Wnt/β-catenin pathway is also activated in the blood islands in Xenopus. Furthermore, Wnt-reporter activity was also detected in the blood islands of the mouse yolk sac. By using morpholino-mediated depletion in Xenopus, we identified Wnt4 as the ligand that is expressed in the mesoderm of the ventral blood island and is essential for the expression of hematopoietic and erythroid marker genes. Injection of an inducible Wnt-interfering construct further showed that, during gastrulation, Wnt/β-catenin signaling is required both in the mesoderm and in the overlying ectoderm for the formation of the ventral blood island. Using recombination assays with embryonic explants, we document that ectodermal BMP4 expression is dependent on Wnt4 signals from the mesoderm. Our results thus reveal a unique role for Wnt4-mediated canonical signaling in the formation and maintenance of the ventral blood island in Xenopus.
脊椎动物原始（胚胎）血液的形成是由不同组织层之间时空限制的信号转导介导的。在非洲爪蟾中，原始血液起源于腹血岛，这涉及到外胚层分泌骨形态发生蛋白（BMP）配体，在原肠胚形成过程中向下面的中胚层发出信号。使用新型转基因报告基因系，我们报告说，经典的 Wnt/β-catenin 途径也在非洲爪蟾的血岛中被激活。此外，在小鼠卵黄囊的血岛中也检测到 Wnt 报告基因的活性。通过在非洲爪蟾中使用基于 morpholino 的耗尽实验，我们确定 Wnt4 是在腹血岛中中胚层表达的配体，对于造血和红细胞标记基因的表达是必需的。Wnt 干扰构建体的诱导注射进一步表明，在原肠胚形成过程中，Wnt/β-catenin 信号通路在中胚层和覆盖的外胚层中对于腹血岛的形成都是必需的。通过胚胎外植体的重组分析，我们记录了外胚层 BMP4 的表达依赖于中胚层的 Wnt4 信号。因此，我们的结果揭示了 Wnt4 介导的经典信号在非洲爪蟾腹血岛的形成和维持中的独特作用。
