Specification of Morphogenetic Pathways Through Differential Regulation of Deformed Target Genes

通过变形靶基因的差异调节来规范形态发生途径

• 批准号: 9514246
• 负责人: James Mahaffey
• 金额: $ 30万
• 依托单位: North Carolina State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-02-01 至 2001-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9514246&HistoricalAwards=false
• 关键词: Specification; Morphogenetic; Pathways; Through; Differential

*** 9514246 Mahaffey, James The long term goal of this project is to understand how certain genes specify regional development in the fruit fly, Drosophila. In particular the specification of anterior-posterior body pattern will be studied. The families of genes to be studies are the homeotic and related hox complex, which specify segment identity in the fly. Though the genetics of this process has been studied extensively, there is very little known about how a specific homeobox gene product (protein) directs the development of a particular segmental morphology. The studies described here will address how differential gene expression and segment identity are specified by the product of the Deformed homeotic gene during maxillary segment development. The studies are designed to elucidate how the Deformed homeoprotein can, in different maxillary cells, specify different genetic pathways determining distinct cell fates. These experiments 1) examine the role of the Deformed homeoprotein and other factors in activating expression of Deformed specific target genes by comparing the regulation of maxillary enhancers from two known target genes and 2) characterize a newly identified gene whose product is necessary, along with Deformed, to activate certain target genes and thereby influence the morphogenetic pathway maxillary cells follow. To examine target gene activation, the role of various factors including the Deformed homeoprotein will be examined by altering the structure of the enhancer region of specific target genes and by analyzing the activity of chimeric enhancers. Further, it is known that two maxillary gene enhancers have differing requirements for a newly identified factor. Genetic analysis indicates that this factor behaves as a cofactor with one gene allowing selective activation of certain target genes thereby influencing which developmental pathway certain cells will follow. A genetic and molecular study of the gene encoding the new factor will be undertaken to determine it s structure and its influence on target homeobox genes required for formation of maxillary appendages. ***

*9514246马哈菲，詹姆斯这个项目的长期目标是了解果蝇的某些基因是如何指定区域发育的。特别是，将研究身体前后部模式的规范。待研究的基因家族是同源异型和相关的HOX复合体，它们规定了果蝇的片段特性。虽然这一过程的遗传学已经得到了广泛的研究，但关于特定的同源框基因产物(蛋白质)如何指导特定节段形态的发育还知之甚少。这里描述的研究将解决如何在上颌骨节段发育过程中由畸形的同源异形基因的产物来确定差异基因表达和节段同一性。这些研究旨在阐明变形的同源蛋白如何在不同的上颌细胞中指定不同的遗传路径，决定不同的细胞命运。这些实验1)通过比较两个已知靶基因上颌骨增强子的调控，检测变形的同源蛋白和其他因素在激活变形的特定靶基因表达中的作用；2)表征新发现的基因，其产物与变形的基因一起激活特定的靶基因，从而影响上颌细胞的形态发生途径。为了检测靶基因的激活，将通过改变特定靶基因的增强子区域的结构和分析嵌合增强子的活性来检测包括变形的同源蛋白在内的各种因素的作用。此外，已知两种上颌基因增强子对新发现的因子有不同的要求。遗传分析表明，该因子与一个基因协同作用，允许选择性地激活某些靶基因，从而影响某些细胞的发育路径。将对编码该新因子的基因进行遗传学和分子研究，以确定其S结构及其对上颌附件形成所需的靶同源框基因的影响。***