Brachyury-downstream gene networks in the notochord

脊索中的 Brachyury 下游基因网络

• 批准号: 7097798
• 负责人: ANNA DI GREGORIO
• 金额: $ 34.57万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7097798
• 关键词: Tunicata; animal genetic material tag; binding sites; biochemical evolution; developmental genetics; electroporation; embryogenesis; genetic enhancer element; genetic regulation; genetic regulatory element; mesoderm; microarray technology; molecular genetics; spine; transcription factor; tropomyosin

DESCRIPTION (provided by applicant): The role of the transcription factor Brachyury (Bra) in notochord formation is well documented and evolutionarily conserved throughout the chordate phylum. However, still little is known about the transcription factors controlled directly or indirectly by Bra and about the function of factors acting in concert with Bra in notochord development and evolution. In particular, the knowledge of structure, common features and modalities of regulation of cis-regulatory modules (enhancers) directing expression in the notochord is fragmentary and poor. We have exploited the experimental advantages offered by the ascidian Ciona intestinalis as a model system to isolate and characterize a collection of notochord enhancers from genes that have already been described as Bra targets and from genes whose relationship with Bra is unknown. Our preliminary data, gathered from the comparative analysis of the notochord enhancers, lead us to hypothesize that notochord formation in Ciona relies upon additional, mostly uncharacterized notochord transcription factors that fall into two categories: Bra-downstream factors, controlled directly or indirectly by Bra and acting as its transcriptional intermediaries and factors acting in concert with Bra. We will test these hypotheses through the following specific aims: (1) Isolate minimal regulatory sequences necessary for notochord expression; (2) Identify the activators controlling the minimal enhancer sequences and study their role in notochord development; (3) Identify the enhancers controlling, in turn, selected notochord activators. The broad scope of the proposed research is to rapidly untangle the gene networks underlying the different steps of notochord development and differentiation and to gain valuable insights into the molecular mechanisms controlling gene expression in the notochord during its formation and evolution.

描述（由申请人提供）：在整个Chordate Phylum中，记录得很好地证明了转录因子Brachyury（BRA）在诺修的形成中的作用。然而，关于直接或间接通过胸罩控制的转录因子以及与胸罩开发和进化中作用的因素的功能，对转录因子的作用知之甚少。特别是，指导脊索中指导表达的顺式调节模块（增强子）的结构，共同特征和方式的知识是碎片和差的。我们已经利用了海藻肠肠肠肠杆菌提供的实验优势作为模型系统，以隔离和表征诺修（Notochord Enhancers）的集合，这些基因与已经被描述为胸罩靶标的基因以及与胸罩的关系尚不清楚的基因。我们的初步数据是从脊索增强剂的比较分析中收集的，这使我们假设Ciona中的脊索形成依赖于其他，主要是未表征的脊索转录因子，这些因素属于两个类别：BRA-DOWNSTREAM因子，由BRA和BRA和BRA和BRA和BRA和间接控制。充当其转录中介机构和与BRA协同作用的因素。我们将通过以下特定目的检验这些假设：（1）孤立的最小调节序列固定表达所需的最小调节序列； （2）确定控制最小增强子序列的激活剂并研究其在脊索发展中的作用； （3）依次确定控制选定的脊索激活剂的增强剂。 拟议研究的广泛范围是迅速解开诺修（Nochord Development）和分化不同步骤的基因网络，并在其形成和进化过程中对控制基因表达的分子机制获得有价值的见解。