Bertrand Vincent, Hudson Clare, Caillol Danielle, Popovici Cornel, Lemaire Patrick
Laboratoire de Génétique et Physiologie du Développement, IBDM, CNRS/INSERM, Université de la Méditerranée/AP de Marseille, Parc Scientifique de Luminy, Case 907, F-13288, Marseille Cedex 9, France.
Cell. 2003 Nov 26;115(5):615-27. doi: 10.1016/s0092-8674(03)00928-0.
In chordates, formation of neural tissue from ectodermal cells requires an induction. The molecular nature of the inducer remains controversial in vertebrates. Here, using the early neural marker Otx as an entry point, we dissected the neural induction pathway in the simple embryos of Ciona intestinalis. We first isolated the regulatory element driving Otx expression in the prospective neural tissue, showed that this element directly responds to FGF signaling and that FGF9/16/20 acts as an endogenous neural inducer. Binding site analysis and gene loss of function established that FGF9/16/20 induces neural tissue in the ectoderm via a synergy between two maternal response factors. Ets1/2 mediates general FGF responsiveness, while the restricted activity of GATAa targets the neural program to the ectoderm. Thus, our study identifies an endogenous FGF neural inducer and its early downstream gene cascade. It also reveals a role for GATA factors in FGF signaling.
在脊索动物中,外胚层细胞形成神经组织需要诱导。在脊椎动物中,诱导物的分子本质仍存在争议。在这里,我们以早期神经标记物Otx为切入点,剖析了海鞘简单胚胎中的神经诱导途径。我们首先分离出在前体神经组织中驱动Otx表达的调控元件,表明该元件直接对FGF信号作出反应,且FGF9/16/20作为内源性神经诱导物发挥作用。结合位点分析和基因功能缺失实验证实,FGF9/16/20通过两个母体反应因子之间的协同作用在外胚层中诱导神经组织形成。Ets1/2介导一般的FGF反应性,而GATAa的受限活性将神经程序靶向到外胚层。因此,我们的研究确定了一种内源性FGF神经诱导物及其早期下游基因级联反应。它还揭示了GATA因子在FGF信号传导中的作用。