MOLECULAR MECHANISMS IN DEVELOPMENT

发展中的分子机制

• 批准号: 3278445
• 负责人: THOMAS B. KORNBERG
• 金额: $ 25.86万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-03-01 至 1993-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3278445
• 关键词: DNA binding protein; Drosophilidae; Escherichia coli; alleles; animal population genetics; cell differentiation; developmental genetics; early embryonic stage; embryogenesis; gene expression; genetic library; genetic manipulation; genetic mapping; genetic promoter element; genetic strain; genetic transcription; larva; metamorphosis; molecular cloning; monoclonal antibody; mutant; nonmammalian vertebrate embryology; nucleic acid probes; nucleic acid sequence; radiotracer; regulatory gene; transcription factor

The developmental mutants of Drosophila melanogaster have been a rich and productive source for investigations into basic mechanisms of development. Indeed, the explosive progress in our understanding of the molecular events in early Drosophila embryogenesis already justified the extensive investments in basic genetic and developmental studies that have provided the requisite materials and conceptual foundation. This progress also justifies our optimism that the Drosophila system will continue to provide valuable insights. We have chosen to intensively study one such locus in Drosophila, engrailed. Studies of mutants indicate that the engrailed function is essential during the precellular stages of embryogenesis for the formation of the blastoderm, during the gastrulation period for normal segmentation, and throughout subsequent development for maintenance of the segmental and compartmental subdivisions. The gene has been cloned, the gene structure and transcription unit has been defined, and the engrailed protein has been isolated. This system is now poised for molecular and enzymological studies to establish how the gene is regulated to effects to precise a program of positional and temporal expression, and to determine how the engrailed protein performs its several roles. We will approach these goals by: (1) isolating cis and trans acting mutations that affect the regulation of the engrailed gene; (2) analyzing the cis regulatory elements of the engrailed promoter by DNA transformation, and by isolating and characterizing the enzymes that regulate transcription of the engrailed gene; and (3) studying the activities and behavior of the engrailed protein.

黑腹果蝇的发育突变体 研究基本机制的丰富而富有成效的资源 的发展。 事实上，我们的爆炸性进步 了解早期果蝇的分子事件 胚胎发生已经证明了在基础设施方面的广泛投资是合理的 遗传和发育研究提供了必要的 材料和概念基础。 这一进步也证明了 我们乐观地认为果蝇系统将继续提供 有价值的见解。 我们选择深入研究果蝇中的一个这样的基因座， 被钉住了。 对突变体的研究表明，engrailed 功能 在胚胎发生的细胞前阶段至关重要 胚盘的形成，在原肠胚期 正常的分割，以及整个后续的开发 维护分段和隔室细分。 这 基因已被克隆，基因结构和转录单位已确定 已被定义，并且被捕获的蛋白质已被分离。 这 系统现已准备好进行分子和酶学研究 确定基因如何被调节以影响精确的程序 位置和时间表达，并确定如何 嵌入蛋白质发挥其多种作用。 我们将通过以下方式实现这些目标：(1) 隔离顺式和反式 影响被吸引基因调节的作用突变； (2)分析enraged启动子的顺式调控元件 通过 DNA 转化，并通过分离和表征 调节嵌入基因转录的酶；和（3） 研究被捕获蛋白质的活性和行为。