Characterization of SoxB genes in neural development

SoxB 基因在神经发育中的表征

• 批准号: 7014060
• 负责人: ELENA M Silva
• 金额: $ 28.04万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-15 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7014060
• 关键词: Xenopus; cell differentiation; computer assisted sequence analysis; developmental genetics; developmental neurobiology; ectoderm; embryogenesis; gel mobility shift assay; gene expression; genetic library; genetic regulatory element; neurogenesis; neurogenetics; nonhistone nucleoprotein; nonmammalian vertebrate embryology; nucleic acid sequence; protein sequence; protein structure function; reporter genes; tissue /cell culture; transcription factor; transfection

DESCRIPTION (provided by applicant): The study of neural induction addresses a fundamental question, in development: How is the fate of ectodermal cells directed toward the formation of neural tissue and away from the formation of epidermis? Answering this question has led to much interest in elucidating the signal transduction pathways involved in the formation and patterning off the vertebrate nervous system. A number of molecules have been defined that are involved in neural formation, but many steps in the pathways remain unknown. Two proteins expressed early in response to neural induction are Sox2 and Sox3, members of the Sox family of HMG box transcription factors. These proteins have been implicated in maintaining a neural progenitor population; both genes are expressed in proliferating neural cells and down-regulated when these cells differentiate into specific neural cell types. By studying their regulation and function we will identify steps necessary for the induction, proliferation and differentiation of neural tissue. Our Specific Aims are to: (1) identify cis-regulatory modules of Sox2 and -3 using 'promoter bashing' and transgenesis (2) identify regulatory factors that interact with the cis sequences of these genes through the candidate gene approach and (3) use gain and loss of function studies to characterize their roles in neural induction and proliferation. These studies will be done in Xenopus laevis and X. tropicalis as much of our knowledge of neural formation comes from embryological studies on the frog and improved transgenic capabilities allow for the rapid identification of regulatory elements and networks. Combined with molecular assays and comparative computational analysis we will study the regulation of Xenopus Sox2 and 3 and define their role in neural development.

描述（由申请人提供）：神经诱导的研究解决了一个基本问题，在开发中：外胚层细胞的命运如何针对神经组织的形成并远离表皮形成？ 回答这个问题引起了极大的兴趣阐明涉及地层的信号转导途径并使脊椎动物神经系统模仿。已经定义了许多参与神经形成的分子，但是途径中的许多步骤仍然未知。在响应神经诱导的早期表达的两种蛋白质是Sox2和Sox3，这是HMG盒转录因子的Sox家族的成员。这些蛋白质与维持神经祖细胞群有关。两种基因在增殖的神经细胞中都表达，当这些细胞分化为特定的神经细胞类型时，下调。 通过研究其调节和功能，我们将确定神经组织诱导，增殖和分化所需的步骤。 我们的具体目的是：（1）使用“启动子扑打”和转基因确定SOX2和-3的顺式调节模块（2）确定与候选基因方法与这些基因的顺式序列相互作用的调节因素，以及（3）使用功能的增益和功能研究来表征其在神经诱导和增殖中的角色。这些研究将在Xenopus laevis和X. topicalis中进行，因为我们对神经形成的了解大部分来自对青蛙的胚胎学研究，而改善的转基因能力可以快速鉴定调节性元素和网络。结合分子测定和比较计算分析，我们将研究爪蟾Sox2和3的调节，并定义它们在神经发育中的作用。