Gene profiling during neural induction in Xenopus laevis:: regulation of BMP signaling by post-transcriptional mechanisms and TAB3, a novel TAK1-binding protein
Gene profiling during neural induction in Xenopus laevis:: regulation of BMP signaling by post-transcriptional mechanisms and TAB3, a novel TAK1-binding protein
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DOI：
10.1242/dev.00097
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发表时间：
2002-12-01
期刊：
影响因子：
4.6
通讯作者：
Brivanlou, AH
中科院分区：
文献类型：
--
作者：
Muñoz-Sanjuán, I;Bell, E;Brivanlou, AH
脊椎动物神经发育的最早决定是胚胎外胚层获得神经特性。细胞。神经诱导的默认模型假设脊椎动物胚胎中的神经命运规范是通过抑制原肠胚外胚层中的表皮诱导信号而发生的。骨形态发生蛋白 (BMP) 充当表皮诱导剂，所有已鉴定的直接神经诱导剂均可阻断细胞内或细胞外的 BMP 信号传导。尽管分泌型神经诱导剂的作用机制已被阐明，但细胞内 BMP 抑制剂在神经诱导中的相关性尚不清楚。为了解决这个问题并确定 BMP 抑制后的下游靶标，我们使用 Xenopus ldevis 5000 克隆原肠胚阶段 cDNA 微阵列监测了由 Smad7 神经化的外胚层外植体中的转录变化。我们报告了 142 个基因的识别和初步表征，这些基因的转录谱在神经化外植体中发生了变化。为了解决阵列中识别的基因在神经诱导过程中的潜在参与，我们在外胚层外植体中进行了功能获得研究。这种方法导致鉴定出四个可以在非洲爪蟾中充当神经诱导剂的基因，以及其他三个可以与已知的神经诱导剂协同作用以促进神经命运的基因。基于这些研究，我们提出了脊椎动物神经诱导过程中基因表达转录后控制的作用，并提出了一种模型，通过一种新型 TAK1 结合蛋白 (TAB3) 调节 TGFbeta 激活激酶 (TAK1) 活性，部分地促进持续 BMP 抑制。
The earliest decision in vertebrate neural development is the acquisition of a neural identity by embryonic ectodermal. cells. The default model for neural induction postulates that neural fate specification in the vertebrate embryo occurs by inhibition of epidermal inducing signals in the gastrula ectoderm. Bone morphogenetic proteins (BMPs) act as epidermal inducers, and all identified direct neural inducers block BMP signaling either intra- or extracellularly. Although the mechanism of action of the secreted neural inducers has been elucidated, the relevance of intracellular BMP inhibitors in neural induction is not clear. In order to address this issue and to identify downstream targets after BMP inhibition, we have monitored the transcriptional changes in ectodermal explants neuralized by Smad7 using a Xenopus ldevis 5000-clone gastrula-stage cDNA microarray. We report the identification and initial characterization of 142 genes whose transcriptional profiles change in the neuralized explants. In order to address the potential involvement during neural induction of genes identified in the array, we performed gain-of-function studies in ectodermal explants. This approach lead to the identification of four genes that can function as neural inducers in Xenopus and three others that can synergize with known neural inducers in promoting neural fates. Based on these studies, we propose a role for post-transcriptional control of gene expression during neural induction in vertebrates and present a model whereby sustained BMP inhibition is promoted partly through the regulation of TGFbeta activated kinase (TAK1) activity by a novel TAK1-binding protein (TAB3).