MOLECULAR CHARACTERIZATION OF THE DORSAL MORPHOGEN

细胞信号分子和调节因子的梯度普遍用于各种图案 后生动物的发育过程。例如，Sonic Hedgehog渐变指定了不同的 脊椎动物胚胎神经管中的神经细胞类型，以及形成 果蝇幼虫翅膀形象盘的发育。Toll-背部信号通路代表了 在动物发育中最彻底地描述了梯度系统。 这项拟议的研究代表了我们继续努力确定背部调节梯度如何 在果蝇早期胚胎中产生基因表达和组织分化的多个阈值。 该研究计划包括三个具体目标，第一，我们将检测背部靶基因的活性 在最近的全基因组微阵列分析中被鉴定出来。在新发现的基因中， 测试对象是Eiger和Mes4，前者是果蝇基因组中的主要肿瘤坏死因子同源物，后者编码一种组织特异性的 CACAAT-box结合蛋白复合体的亚基，Nf-Y。第二，我们将结合使用 生物信息学方法和转基因试验来确定背部倾斜度如何调节表达 以浓度依赖的方式对不同的靶基因进行比较。特别努力将集中在定义“独联体-- 监管代码“，由此协调监管的靶标增强剂共享一种特有的因子组合 结合部位，包括背部和额外的，主要未知的调节因子的结合部位。第三，我们 将决定在感染或受伤时诱导的免疫基因是否共享类似的组织 顺式监管要素。特别的努力将集中在背部相关基因的激活上。 免疫基因，Dif和Dresish，以及GATA转录因子，蛇。

Gradients of cell signaling molecules and regulatoryfactorsare pervasivelyused in a variety of patterning process in metazoan development. Examples include the Sonic Hedgehog gradient that specifies different neuronal cell types in the neural tube of vertebrateembryos,and the Dpp gradient that patterns the developing wing imaginal disk in Drosophila larvae. The Toll-Dorsal signaling pathway represents one of the most thoroughly characterized gradient systemsin animal development. The proposed study represents a continuationof our efforts to determine how the Dorsal regulatorygradient produces multiple thresholds of gene expression and tissue differentiation in the early Drosophila embryo. The research plan includes 3 specific aims, First, we will examine the activitiesof Dorsal target genes that were identified in recent whole-genome microarray assays. Among the newly identified genes that will be tested is Eiger, the major TNF homolog in the Drosophila genome, and Mes4, which encodes a tissue-specific subunit of the CACAAT-box binding protein complex, NF-Y. Second, we will use a combination of bioinformatics methods and transgenic assays to determine how the Dorsal gradient regulates the expression of different target genes in a concentration-dependent manner. Particular efforts will focus on defining a"cis- regulatory code", whereby coordinately regulated target enhancers share a characteristic combination of factor binding sites, including binding sites for Dorsal and additional,mainlyunknown regulatory factors. Third, we will determine whether immunity genes that are induced upon infection or injury share a similar organization of cis-regulatory elements. Particular efforts will focus on genes that are activated by the Dorsal-related immunity genes, Dif and Relish, and the GATA transcriptionfactor, Serpent.