Distinct regulatory elements direct Delta 1 expression in the nervous system and paraxial mesoderm of transgenic mice
Distinct regulatory elements direct Delta 1 expression in the nervous system and paraxial mesoderm of transgenic mice
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DOI：
10.1016/s0925-4773(00)00322-1
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发表时间：
2000-07-01
影响因子：
2.6
通讯作者：
Gossler, A
中科院分区：
文献类型：
--
作者：
Beckers, J;Caron, A;Gossler, A
Delta1基因编码小鼠中的Notch配体之一。Delta1在胚胎发生早期以复杂和动态的模式在近轴中胚层和神经外胚层中表达，并且对于正常的体节发生和神经元分化是必需的。在不同物种中已经鉴定出被认为响应于配体结合和Notch活化而起作用的分子组分。相反，Notch受体及其配体的转录调控知之甚少。作为第一步，以确定在不同的组织中的Delta1表达的上游调控因子，我们搜索的Delta1启动子中的顺式调控区域能够指导异源基因表达的组织特异性的方式在转基因小鼠。我们的研究结果表明，一个4.3 kb的基因组DNA片段的Delta1基因是足够的lacZ报告转基因复制Delta1表达的大部分方面，从原条阶段到早期器官形成，使用最小的Delta1启动子，我们还表明，这个上游区域包含不同的调控模块，单独指导组织特异性转基因表达的内源性表达模式的亚结构域。看来，在近轴中胚层的表达取决于多个积极和消极的调控元件的相互作用。我们还发现，在哺乳动物和硬骨鱼的进化过程中，至少有一些所需的神经管的亚结构域中的转基因表达的调控序列一直保持，这表明控制Delta基因表达的调控网络的一部分可能是保守的。(C)2000爱思唯尔科学爱尔兰有限公司保留所有权利。
The Delta1 gene encodes one of the Notch ligands in mice. Delta1 is expressed during early embryogenesis in a complex and dynamic pattern in the paraxial mesoderm and neuroectoderm, and is essential for normal somitogenesis and neuronal differentiation. Molecular components thought to act in response to ligand binding and Notch activation have been identified in different species. In contrast, little is known about the transcriptional regulation of Notch receptors and their ligands. As a first step to identify upstream factors regulating Delta1 expression in different tissues, we searched for cis-regulatory regions in the Delta1 promoter able to direct heterologous gene expression in a tissue specific manner in transgenic mice. Our results show that a 4.3 kb genomic DNA fragment of the Delta1 gene is sufficient in a lacZ reporter transgene to reproduce most aspects of Delta1 expression from the primitive streak stage to early organogenesis, Using a minimal Delta1 promoter we also show that this upstream region contains distinct regulatory modules that individually direct tissue-specific transgene expression in subdomains of the endogenous expression pattern. It appears that expression in the paraxial mesoderm depends on the interaction of multiple positive and negative regulatory elements. We also find that at least some regulatory sequences required for transgene expression in subdomains of the neural tube have been maintained during the evolution of mammals and teleost fish, suggesting that part of the regulatory network that controls expression of Delta genes may be conserved. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.