Transcriptional Regulation of Mesoderm Development

中胚层发育的转录调控

• 批准号: 6837744
• 负责人: ANN K CORSI
• 金额: $ 13.5万
• 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 2006-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6837744
• 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：（由申请人提供）研究目标是阐明 转录级联反应参与中胚层模式和发展， 线虫秀丽隐杆线虫假设两个基本的 螺旋-环-螺旋转录因子CeTwist和CeE/DA， 将测试影响中胚层命运和功能的靶基因。具体 目的1将研究CeTwist，CeE/DA和未知的遗传相互作用。 通过进行基因筛选， CeTwist基因的一个特殊等位基因的抑制子。具体目标2，DNA 微阵列将与从过度表达 CeTwist和CeEDA鉴定下游靶基因， 随后进行了表征。这些研究与医学相关，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过早 颅缝融合称为颅缝早闭。类似的缺陷被发现在 与下游Twist靶基因相关的其他综合征， C elegans中的同源物。在大约100种相关的颅缝早闭症中， 被认为是由单基因疾病引起的，而一个特定的基因已经被 在不到10种疾病中发现。新的基因在这条途径中， 在秀丽线虫中发现的基因被预测是未知基因的良好候选者 这些人类疾病的遗传基础

项目成果

Distinct Caenorhabditis elegans HLH-8/twist-containing dimers function in the mesoderm.

• DOI: 10.1002/dvdy.23734
• 发表时间: 2012-03
• 期刊: Developmental dynamics : an official publication of the American Association of Anatomists
• 作者: Philogene MC;Small SG;Wang P;Corsi AK
• 通讯作者: Corsi AK

C. elegans twist gene expression in differentiated cell types is controlled by autoregulation through intron elements.

• DOI: 10.1016/j.ydbio.2010.07.025
• 发表时间: 2010-10-15
• 期刊: Developmental biology
• 影响因子: 2.7
• 作者: Meyers SG;Corsi AK
• 通讯作者: Corsi AK