Specification of Morphogenetic Pathways Through Differential Regulation of Deformed Target Genes

* 9514246马哈菲，詹姆斯 该项目的长期目标是了解某些基因如何指定果蝇（Drosophila）的区域发育。特别是前-后体模式的规格将进行研究。待研究的基因家族是同源异型和相关的hox复合体，它在果蝇中指定片段身份。虽然这一过程的遗传学已经被广泛研究，但对于特定同源异型盒基因产物（蛋白质）如何指导特定节段形态的发育知之甚少。 这里描述的研究将解决如何差异基因表达和节的身份是指定的产品的变形同源异型基因在上颌节的发展。这些研究旨在阐明变形同源异型蛋白如何在不同的上颌细胞中指定不同的遗传途径来决定不同的细胞命运。这些实验1）通过比较来自两种已知靶基因的上颌增强子的调节来检查变形同源异型蛋白和其它因子在激活变形特异性靶基因的表达中的作用，和2）表征新鉴定的基因，其产物是激活某些靶基因所必需的，沿着变形，从而影响上颌细胞遵循的形态发生途径。 为了检查靶基因的激活，将通过改变特定靶基因的增强子区域的结构和通过分析嵌合增强子的活性来检查包括变形同源异型蛋白在内的各种因子的作用。此外，已知两种上颌基因增强子对新鉴定的因子具有不同的要求。遗传分析表明，该因子作为一个辅因子与一个基因，允许选择性激活某些靶基因，从而影响某些细胞将遵循的发育途径。将对编码新因子的基因进行遗传和分子研究，以确定其结构及其对上颌附属物形成所需的靶同源框基因的影响。 ***

*** 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. ***