GENETIC CONTROL OF DEVELOPMENTAL PATHWAYS

发育途径的遗传控制

• 批准号: 2872778
• 负责人: EDWARD B LEWIS
• 金额: $ 15.96万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-01-01 至 2000-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2872778
• 关键词: Drosophilidae; biochemical evolution; developmental genetics; gene deletion mutation; gene expression; gene interaction; genetic manipulation; genetic regulatory element; growth /development; homeobox genes; thorax

The long-term objectives are to understand (l) how the genes of the homeotic gene complex (HOM-C) and its cis-regulatory regions program the develop of the head, thorax and abdomen of higher organisms, and (2) why the complexes have been able to remain intact for a time period estimated to predate the separation of the vertebrates and invertebrates, estimated to be over 500 million years. The proposal concentrates on determining how the cis- regulatory regions of the bithorax complex (BX-C) in Drosophila interact with one another to bring about the regulation of the protein-coding genes of the complex. The specific aims are (1) to dissect the genetic basis for the colinearity of the genes; namely, that their order in the chromosome parallels their order of expression along the antero-posterior body axis of the organism -- a rule that is now known to apply not only to Drosophila but to all vertebrates studied, including human beings; (2) to understand the basis of two highly unusual phenomena, cis-overexpression (COE) and cis-inactivation (CIN), that underlie the regulation of the genes of the BX-C; and (3) to make use of deletions within specific cis- regulatory regions to determine, by means of classical cis-trans tests, the degree to which the two abdominal domains of the complex (abd-A and Abd-B) require proximity for their normal functioning. The experiments proposed involve using x-rays to generate (l) modifiers that are expected to enhance and in other cases to suppress specific COE effects and, indirectly, CIN effects, and (2) deletions of specific cis-regulatory regions. Ultimately, the research has implications for understanding the basis of genetically determined developmental abnormalities, including birth defects and cancer, when these are brought about by mutations in the master control genes which make up the HOM-C.

长期目标是了解 (l) 基因如何 同源异型基因复合体（HOM-C）及其顺式调控区 规划高等动物头部、胸部和腹部的发育 有机体，以及（2）为什么这些复合物能够保留下来 估计在分离之前的一段时间内完好无损 脊椎动物和无脊椎动物，估计超过 5 亿 年。该提案的重点是确定如何顺 果蝇双胸复合体 (BX-C) 的调节区 相互作用，以实现监管 复合物的蛋白质编码基因。具体目标是 (1) 剖析基因共线性的遗传基础；即， 它们在染色体中的顺序与它们的顺序平行 沿着生物体前后体轴的表达—— 现在已知这一规则不仅适用于果蝇，而且适用于所有动物 研究的脊椎动物，包括人类； （2）了解 两种非常不寻常的现象的基础，顺式过度表达（COE）和 顺式失活（CIN），是基因调控的基础 BX-C 的； (3) 利用特定顺式内的删除 通过经典的顺式-反式确定调节区域 测试，复合体的两个腹部域的程度 （abd-A 和 Abd-B）需要靠近才能正常运作。 提出的实验涉及使用 X 射线来生成 (l) 预期会增强的修饰符，在其他情况下会增强 抑制特定的 COE 效应，并间接抑制 CIN 效应，以及 (2) 特定顺式调控区域的删除。最终， 研究对于理解其基础具有重要意义 遗传决定的发育异常，包括 由突变引起的出生缺陷和癌症 在构成 HOM-C 的主控基因中。