Distinct roles for Fgf, Wnt and retinoic acid in posteriorizing the neural ectoderm.
Distinct roles for Fgf, Wnt and retinoic acid in posteriorizing the neural ectoderm.
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DOI：
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发表时间：
2002-09
期刊：
影响因子：
4.6
通讯作者：
T. Kudoh;Stephen W. Wilson;I. Dawid
中科院分区：
文献类型：
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作者：
T. Kudoh;Stephen W. Wilson;I. Dawid
脊椎动物早期的神经模式包括抑制新生神经板前(A)和促进后(P)位置值的信号。在这项研究中，我们研究了维甲酸（RA）、Fgf和Wnt信号在促进外胚层后命运中的作用及其相互作用。我们分析了编码维甲酸4-羟化酶的基因cyp26/P450RAI的表达和功能，作为研究这些事件的工具。Cyp26首先在囊胚晚期的前神经外胚层和囊胚边缘表达。当后神经基因hoxb1b在原肠胚形成期间表达时，它与cyp26表现出明显的互补模式。使用这两个基因，以及otx2和meis3作为前、后标记，我们发现Fgf和Wnt信号抑制前基因的表达，包括cyp26。cyp26过表达抑制后缘基因，提示cyp26的前缘表达对于限制后缘基因的表达具有重要作用。与此一致的是，morpholino寡核苷酸敲低cyp26会导致后基因的前扩张。我们进一步表明，Fgf-和wnt依赖性后基因的激活是由RA介导的，而前基因的抑制不依赖于RA信号传导。Fgf和Wnt信号抑制cyp26的表达，而cyp26抑制RA信号。由此可见，cyp26在连接Fgf、Wnt和RA信号调控斑马鱼囊胚晚期神经外胚层向原肠胚胚的AP模式中具有重要作用。
Early neural patterning in vertebrates involves signals that inhibit anterior (A) and promote posterior (P) positional values within the nascent neural plate. In this study, we have investigated the contributions of, and interactions between, retinoic acid (RA), Fgf and Wnt signals in the promotion of posterior fates in the ectoderm. We analyze expression and function of cyp26/P450RAI, a gene that encodes retinoic acid 4-hydroxylase, as a tool for investigating these events. Cyp26 is first expressed in the presumptive anterior neural ectoderm and the blastoderm margin at the late blastula. When the posterior neural gene hoxb1b is expressed during gastrulation, it shows a strikingly complementary pattern to cyp26. Using these two genes, as well as otx2 and meis3 as anterior and posterior markers, we show that Fgf and Wnt signals suppress expression of anterior genes, including cyp26. Overexpression of cyp26 suppresses posterior genes, suggesting that the anterior expression of cyp26 is important for restricting the expression of posterior genes. Consistent with this, knock-down of cyp26 by morpholino oligonucleotides leads to the anterior expansion of posterior genes. We further show that Fgf- and Wnt-dependent activation of posterior genes is mediated by RA, whereas suppression of anterior genes does not depend on RA signaling. Fgf and Wnt signals suppress cyp26 expression, while Cyp26 suppresses the RA signal. Thus, cyp26 has an important role in linking the Fgf, Wnt and RA signals to regulate AP patterning of the neural ectoderm in the late blastula to gastrula embryo in zebrafish.