Transcriptional Regulation of Mesoderm Development

中胚层发育的转录调控

• 批准号: 6460625
• 负责人: ANN K CORSI
• 金额: $ 13.05万
• 依托单位: CATHOLIC UNIVERSITY OF AMERICA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6460625
• 关键词: Caenorhabditis elegans; DNA binding protein; craniosynostosis; developmental genetics; gene induction /repression; gene mutation; genetic mapping; genetic regulation; genetic regulatory element; genetic susceptibility; genetic transcription; genetically modified animals; histogenesis; intermolecular interaction; invertebrate embryology; mesoderm; microarray technology; molecular cloning; molecular pathology; reporter genes; suppressor mutations

DESCRIPTION: (provided by applicant) The research goal is to elucidate a transcriptional cascade involved in mesodermal patterning and development in the nematode Caenorhabditis elegans. The hypothesis that two basic helix-loop-helix transcription factors, CeTwist and CeE/DA, together activate target genes that affect mesodermal fate and function will be tested. Specific Aim 1 will investigate the genetic interactions of CeTwist, CeE/DA, and unknown proteins at target promoters by performing a genetic screen designed to find suppressors of a special allele of the CeTwist gene. In Specific Aim 2, DNA microarrays will be hybridized with RNA made from animals overexpressing CeTwist and CeEDA to identify downstream target genes which will be subsequently characterized. These studies are medically relevant because individuals with mutations in the human Twist gene are afflicted with Saethre-Chotzen syndrome. This syndrome is characterized by the premature fusion of cranial sutures called craniosynostosis. Similar defects are found in other syndromes associated with downstream Twist target genes that have homologs in C elegans. Out of about 100 related forms of craniosynostosis, 30 are thought to arise from single gene disorders, and a specific gene has been identified in less than 10 disorders. New genes in the pathway that are identified in C elegans are predicted to be good candidates for the unknown genetic basis underlying these human disorders.

描述：(申请人提供)本研究的目的是阐明 转录级联参与中胚层的形成和发育 线虫。假设两个基本的 螺旋-环-螺旋转录因子CeTwist和Cee/DA共同激活 影响中胚层命运和功能的目标基因将被测试。特定的 目标1将研究CeTwist、Cee/DA和未知的遗传交互作用 通过进行基因筛查发现靶启动子上的蛋白质 CeTwist基因一个特殊等位基因的抑制者。在特定目标2中，DNA 微阵列将与从过度表达的动物中提取的RNA杂交 CeTwist和Ceeda识别下游靶基因，这些基因将被 随后描述了它的特征。这些研究具有医学上的相关性，因为 人类Twist基因突变的个体患有 Saethre-Chotzen综合征。这种综合征的特点是早产儿 颅缝融合称为颅缝融合。类似的缺陷也存在于 与下游Twist靶基因相关的其他综合征 线虫中的同源物。在大约100种相关形式的颅缝融合中，30例 被认为是由单基因疾病引起的，而一种特定的基因 在不到10种疾病中被识别。途径中的新基因是 在Celegans中被发现的人被预测是未知的很好的候选者 这些人类疾病背后的遗传基础。