ESTABLISHMENT OF THE DORSAL-VENTRAL AXIS IN DROSOPHILA

果蝇胚胎的背腹轴是由一种 诱导线索起源于包绕细胞的体细胞。 发育中的卵母细胞。此归纳提示需要表示 雌性体细胞组织中的母性效应位点管。这个 该基因的活性有助于确定信号的极性 导致背侧核分级摄取的信号转导途径 基因产物，一种转录因子。广泛而长期的目标是 这一建议是为了阐明体细胞的分子性质 归纳线索及其功能和调控方式。这些调查 在两个方面具有医学上的相关性。果蝇胚胎背部- 腹侧极化似乎至少部分是由细胞外引起的 对丝氨酸蛋白分解活性的调节，类似于在 人类的血液凝块形成和补体固定。第二, 调节核局部化是一种普遍的机制 转录因子的调控和背部基因共有的氨基酸 与许多脊椎动物转录因子的序列同源性 活动也是通过这种方式进行监管的。其中之一， 转录因子核因子-kappaB是一种重要的转录调节因子 对免疫系统的影响。为了研究体细胞 卵室上皮控制胚胎的背腹两极 PIPE基因将被克隆和鉴定。它的核苷酸 序列将被确定，时间和空间模式 将对该RNA的表达进行研究。针对目标的抗体 将获得PIPE蛋白产物，免疫组织化学将 被用来研究细胞的空间和亚细胞定位 在背腹模式形成过程中的蛋白质。要确定如何使用 卵室内背腹两极的预先测定 影响胚胎背腹两极、管道RNA和蛋白质 此外，还将研究雌性卵巢的表达模式。 携带着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.