ESTABLISHMENT OF THE DORSAL-VENTRAL AXIS IN DROSOPHILA

果蝇胚胎的背腹轴是由一个 诱导性信号起源于包裹细胞的体细胞滤泡细胞， 发育中的卵母细胞这种归纳提示需要表达 母源效应在雌性体细胞组织中的作用轨迹管道。的 该基因的活性有助于确定信号的极性 转导途径，导致背侧核摄取分级 基因产物，转录因子。广泛的长期目标 这一建议是为了阐明体细胞的分子本质， 归纳线索及其功能和调节。这些调查 在两个方面具有医学相关性。果蝇胚胎背- 腹侧极性似乎至少部分来自细胞外 丝氨酸蛋白水解活性的调节，类似于 血凝块形成和补体结合。第二、 核定位的调节是一种普遍的机制， 转录因子的调控和背侧基因共享氨基酸 与许多脊椎动物转录因子的序列同源性， 活动也以这种方式受到监管。其中之一， 转录因子NF κ B B是一种重要的转录调节因子 免疫系统。为了研究体细胞的机制， 卵室上皮控制胚胎背腹极性 pipe基因将被克隆和表征。其核苷酸 序列将被确定，时间和空间模式的 将研究RNA的表达。针对以下的抗体 将获得pipe蛋白产物，免疫组织化学将 用于研究细胞的空间和亚细胞定位 蛋白质在背腹图案形成。以确定如何 预先确定卵室内的背腹极性 影响胚胎的背腹极性、管状RNA和蛋白质 还将研究雌性卵巢中的表达模式 携带改变卵室极性的突变

The dorsal-ventral axis in the Drosophila embryo is established by an inductive cue originates in the somatic follicle cells that ensheathe the developing oocyte. This inductive cue requires the expression of the maternal effect locus pipe in the somatic tissue of the female. The activity of this gene contributes to defining the polarity of a signal transduction pathway that results in graded nuclear uptake of the dorsal gene product, a transcription factor. The broad, long-term objective of this proposal is to elucidate the molecular nature of the somatic inductive cue and how it functions and is regulated. These investigations have medical relevance in two respects. Drosophila embryonic dorsal- ventral polarity appears to result, at least in part, from extracellular regulation of serine proteolytic activity, similar to what is seen during blood clot formation and complement fixation in humans. Second, regulation of nuclear localization is a general mechanism for the regulation of transcription factors and the dorsal gene shares amino acid sequence homology with a number of vertebrate transcription factors whose activities are also regulated in this way. One of these, the transcription factor NF kappa B is an important transcriptional regulator of the immune system. To investigate the mechanism by which the somatic epithelium of the egg chamber controls embryonic dorsal-ventral polarity polarity the pipe gene will be cloned and characterized. Its nucleotide sequence will be determined and temporal and spatial patterns of expression of the RNA will be investigated. Antibodies directed against the pipe protein product will be obtained and immunohistochemistry will be used to investigate spatial and subcellular localization of the protein during dorsal-ventral pattern formation. To determine how the prior determination of dorsal-ventral polarity in the egg chamber influences embryonic dorsal-ventral polarity, the pipe RNA and protein expression patterns will also be investigated in the ovaries of females carrying mutations which alter the polarity of the egg chamber.