Specification of Morphogenetic Pathways Through Differential Regulation of Deformed Target Genes

Mahaffey， James该项目的长期目标是了解某些基因如何指定果蝇的区域发育。特别是对前后体型的规范进行了研究。待研究的基因家族是同源和相关的hox复合体，它指定了果蝇的片段身份。尽管这一过程的遗传学已被广泛研究，但对于特定的同源盒基因产物（蛋白质）如何指导特定片段形态的发展知之甚少。本文所描述的研究将解决在上颌节发育过程中，畸形同源基因的产物如何指定差异基因表达和节段身份。这些研究旨在阐明畸形同型蛋白如何在不同的上颌细胞中指定不同的遗传途径，决定不同的细胞命运。这些实验1)通过比较两种已知靶基因对上颌增强子的调控，研究了变形同型蛋白和其他因子在激活变形特异性靶基因表达中的作用；2)表征了一个新发现的基因，该基因的产物与变形一样，是激活某些靶基因所必需的，从而影响上颌细胞的形态发生途径。为了研究靶基因的激活，将通过改变特定靶基因的增强子区域结构和分析嵌合增强子的活性来研究包括变形同型蛋白在内的各种因素的作用。此外，已知两个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，该因子作为一个辅助因子与一个基因，允许选择性激活某些靶基因，从而影响某些细胞的发育途径。将对编码该新因子的基因进行遗传和分子研究，以确定其结构及其对形成上颌附属物所需的靶同源盒基因的影响。＊＊＊

*** 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. ***