Mesodermal Wnt signaling organizes the neural plate via Meis3
Mesodermal Wnt signaling organizes the neural plate via Meis3
复制标题
DOI：
10.1242/dev.044750
复制
发表时间：
2010-05-01
期刊：
影响因子：
4.6
通讯作者：
Frank, Dale
中科院分区：
文献类型：
--
作者：
Elkouby, Yaniv M.;Elias, Sarah;Frank, Dale
在脊椎动物中，规范的Wnt信号控制着后脑神经细胞的谱系特征。尽管向神经板发出的WNT信号足以进行后验识别，但这种活动的来源和时间仍不确定。此外，这种活性的关键分子靶点还没有定义。在这里，我们确定了内源性Wnt的活性及其在控制必要的下游转录因子Meis3中的作用。WNT3a在一个特殊的中胚层区域中表达，即近轴背外侧中胚层，它向覆盖的神经外胚层发出信号。该区域合子Wnt3a的缺失不会改变中胚层细胞的命运，但会阻止Meis3在神经外胚层的表达，从而引发后脑神经命运的丧失。异位表达的Meis3蛋白足以挽救这种表型。此外，Wnt3a对后神经系统的诱导需要神经板中有功能的MEIS3。通过芯片和启动子分析，我们证明Meis3是Wnt/β-catenin信号转导的直接靶点。这提出了一种新的神经前后构型模型，在该模型中，来自旁轴中胚层的WNT3a通过直接激活覆盖神经板中的关键转录因子来诱导后部细胞的命运。
In vertebrates, canonical Wnt signaling controls posterior neural cell lineage specification. Although Wnt signaling to the neural plate is sufficient for posterior identity, the source and timing of this activity remain uncertain. Furthermore, crucial molecular targets of this activity have not been defined. Here, we identify the endogenous Wnt activity and its role in controlling an essential downstream transcription factor, Meis3. Wnt3a is expressed in a specialized mesodermal domain, the paraxial dorsolateral mesoderm, which signals to overlying neuroectoderm. Loss of zygotic Wnt3a in this region does not alter mesoderm cell fates, but blocks Meis3 expression in the neuroectoderm, triggering the loss of posterior neural fates. Ectopic Meis3 protein expression is sufficient to rescue this phenotype. Moreover, Wnt3a induction of the posterior nervous system requires functional Meis3 in the neural plate. Using ChIP and promoter analysis, we show that Meis3 is a direct target of Wnt/beta-catenin signaling. This suggests a new model for neural anteroposterior patterning, in which Wnt3a from the paraxial mesoderm induces posterior cell fates via direct activation of a crucial transcription factor in the overlying neural plate.