GENETIC CONTROL OF DEVELOPMENTAL PATHWAYS

发育途径的遗传控制

• 批准号: 3310464
• 负责人: EDWARD B LEWIS
• 金额: $ 19.46万
• 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 1991-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3310464
• 关键词: X ray; abdomen; cell transformation; chromatography; developmental genetics; gene duplication; gene expression; gene redundancy; genetic crossing over; genetic mapping; genetic regulation; histogenesis; radiotracer; regulatory gene; scanning electron microscopy; thorax; tissue mosaicism

The bithorax complex (BX-C) in Drosophila is a model system for studying how genes regulate growth and development. The complex spans over 300 kilobases of DNA and comprises at least nine genes that regulate other genes outside the complex to program much of the development of the thorax and abdomen of the organism. The broad objectives are (1) to determine how the individual genes of the complex are themselves regulated such that they become expressed along the body axis in an order that parallels their order in the chromosome; and (2) to understand the basis of the phenomenon of transvection (or pairing-dependent complementation) that involves an apparent coupling of cis- and trans-regulation. The specific goals are: (1) to identify as many as possible of the specific morphogenetic functions controlled by the BX-C genes and to correlate those functions with the genetic and molecular maps of the complex; [a new methodology, which uses X rays to derive transvection-suppressing rearrangements (TSRs), permits saturating the complex with chromosomal breakages that are unselected with respect to whether they do not or do not contain a mutant lesion in any of the BX-C genes; (2) to analyze regulation, especially in cis, of the BX-C genes themselves, by studying the conditions underlying the cis-inactivation (CIN) and cis-overexpression COE phenomena; (3) to identify the type of DNA-rearrangement involved in the Transabdominal mutant which results in misregulation of one or more genes located distally in the BX-C; and (4) to determine the extent to which transvection occurs throughout the entire complex and the specific conditions which promote or suppress transvection. Health-relatedness: (1) probes derived from portions of the BX-C might be able to identify within the human genome homeotic genes responsible for many types of congenital malformations such as gonadal dysgenesis, and (2) the molecular analysis of the Transabdominal mutant may uncover an important mechanism underlying the induction of certain types of benign tumors that depend upon misregulation of homeotic genes.

果蝇的双胸复合体（BX-C）是研究果蝇的模型系统 基因如何调节生长和发育。 该综合体占地300多 千碱基的 DNA，并包含至少九个调节其他基因的基因 复合体外部的基因对胸部的大部分发育进行编程 和生物体的腹部。 主要目标是 (1) 确定如何 复合体的各个基因本身受到调节，使得它们 沿着身体轴以与其顺序平行的顺序表达 在染色体中； (2)了解现象的基础 横传（或配对依赖性互补）涉及 顺式和反式调节的明显耦合。 具体目标是： (1) 识别尽可能多的特定形态发生功能 由 BX-C 基因控制并将这些功能与 该复合物的遗传和分子图谱； [一种新方法，使用 X 射线产生平移抑制重排（TSR），允许 使复合体充满未选择的染色体断裂 关于它们是否不包含或不包含任何突变病变 BX-C基因； (2) 分析 BX-C 的调节，尤其是顺式调节 基因本身，通过研究其背后的条件 顺式失活（CIN）和顺式过表达 COE 现象； (3) 至 确定涉及经腹的 DNA 重排类型 导致位于远端的一个或多个基因的错误调节的突变体 在BX-C中； (4) 确定平移发生的程度 贯穿整个综合体和促进或促进的具体条件 抑制横传。 健康相关性：(1) 探针源自 BX-C 的部分内容可能能够在人类基因组中进行识别 同源异型基因导致许多类型的先天畸形，例如 作为性腺发育不全，以及（2）经腹的分子分析 突变体可能揭示诱导的重要机制 某些类型的良性肿瘤依赖于同源异型的错误调节 基因。