MOLECULAR GENETICS OF EMBRYONIC POLARITY IN DROSOPHILA

在多细胞生物中， (A-P)胚胎的极性对于随后的 由于整个身体计划是相对于 这个轴。 关于这些分子机制知之甚少， 哪种胚胎极性被建立，以及轴向信息是如何 被转化为细胞命运。 基因和分子分析 表明许多决定胚胎极性的分子 和图案是在卵巢卵泡中由母体合成的。 果蝇是一种很好的生物体， 对发展现象进行突变分析， 分子水平，也具有特定的优势， 卵子发生的研究 这项建议旨在分析基因和 在果蝇卵子发生过程中， 前后胚轴的形成：躯干（9 等位基因）、剪接型（1个等位基因）、外显型（4个等位基因）和双头型（1个等位基因 等位基因）。 总之，这四个基因座的突变表型 包括表型异常的整个范围， 大约20个基因座参与建立A-P轴， 对突变体组合的分析表明， 形成分子相互作用系统的一部分， 说明胚胎的极性。 基因分析将用于 详细描述现有的和新分离的等位基因在这些 基因座，并在高分辨率的细胞遗传学映射它们。 的 分子分析将集中在发现的最多的位点上。 有趣的基因以及最听话的分子。 的 转录本的结构，它们的空间分布和蛋白质- 将确定编码潜力。 与已知的同源性 蛋白质可能表明编码的蛋白质的功能，酶的作用， proteins. 随后，将产生抗融合的抗血清， 蛋白质，并用于分析空间和时间表达 克隆基因的蛋白质产物。 的结果 基因产物的空间分析将具有重要的 与一般发育和细胞生物学问题有关， 空间不对称是如何在细胞中建立的， 限制了图案形成的可能分子模型。 在 对基因产物的长期生化研究及其 活动和互动，应该提供机械的见解， 发展的核心过程之一， 多细胞生物

In multicellular organisms the determination of anterior-posterior (A-P) embryonic poloarity is fundamental to subsequent development since the entire body plan is constructed relative to this axis. Little is known about the molecular mechanisms by which embryonic polarity is established and how axial information is transduced into cell fate. Genetic and molecular analyses have shown that many of the molecules that specify embryonic polarity and pattern are synthesized maternally in the ovarian follicies. Drosophila melanogaster is an excellent organism in which to pursue the mutational analysis of developmental phenomena to the molecular level and also possesses specific advantages for the study of oogenesis. This proposal aims to analyze genetically and molecularly four loci in Drosophila required during oogenesis for the formation of the anterior-posterior embryonic axis: torso (9 alleles), spliced (1 allele), exuperantia (4 alleles) and dicephalic (1 allele). Together, the mutant phenotypes of these four loci encompass the entire range of phenotypic abnormalities of the roughly twenty loci involved in establishing the A-P axis, and analyses of mutant combinations suggest that their gene products form part of an interacting system of molecules involved in specifying embryonic polarity. Genetic analysis will be used to characterize in detail existing and newly isolated alleles at these loci and to map them at high resolution cytogenetically. The molecular analyses will focus on the loci found to be most interesting genetically as well as most tractable molecularly. The structure of the transcripts, their spatial distribution and protein- coding potential will be determined. Homologies to known proteins may suggest functional, enzymatic roles for the encoded proteins. Subsequently, antisera will be raised against fusion proteins and used to analyze the spatial and temporal expression of the protein products of the cloned genes. The results of the spatial analyses of the gene products will have an important bearing on the general developmental and cell biological problem of how spatial asymmetries are established in cells, and will constrain possible molecular models of pattern formation. In the longer term, biochemical studies of the gene products and their activities and interactions, should provide mechanistic insights into one of the central processes in the development of multicellular organisms.