DROSOPHILA PATTERN REPAIR--GENETIC AND CELLULAR ANALYSIS

模式的建立是发育生物学的一个重要主题， 无论是在分子、细胞还是解剖学层面上进行研究。 虽然人们非常重视应用以下工具 分子生物学和遗传学对模式涌现的研究 对花样的维护与维修问题进行了初步研究 从解剖学的角度来看。肢体再生等过程(输入 昆虫和两栖动物)和(昆虫的)想象盘修复就是例子 花纹修复。我们提出了胚胎模式修复的存在 负责检测和修复的系统(PR)基因 果蝇胚胎发育过程中的模式错误。我们有 开始分离和分析影响胚胎模式的突变 修理。 在实验中观察到胚胎模式修复，其中剂量为 母体效应基因BCD(BCD)受到调节。在卵子发生过程中， BCD mRNA定位于卵母细胞的前端。BCD的翻译 受精时的信息导致BCD的浓度梯度 蛋白质，进而触发一系列转录事件， 导致前部结构的规范(复制 在没有BCD活动的情况下观察到后部结构)。 将BCD基因剂量从一份减少或增加到四份，两份 副本是正常的补充物，引起一些前部形态 标记要分别向前或向后移动。一个人会 预计幼虫前部的大小会相应减小或增加 结构或可能降低生存能力。出乎意料的是，两人 这些胚胎类型发育成具有生存能力和 繁殖力与野生型相当。这些观察表明，胚胎 有能力补偿由以下因素引起的图案扰动 BCD渐变的变化。我们就是这种补偿性的反应 归功于花纹修复系统。 图案修复是在什么时候以及如何进行的？为了理解这一点 胚胎对图案缺陷的反应，一个人必须有一个详细的命运图 受影响的区域包括有关细胞迁移的信息， 形状、有丝分裂和死亡。我们已经开发了选择性标记的工具 活胚胎中的单个细胞和跟随它们的行为 发展。此外，我们和其他人已经开发了用于 监测活胚胎中的细胞死亡。有了如此详细的命运地图， 野生型胚胎，我们将能够确定细胞的变化 模式修复过程中的行为。 模式修复涉及哪些基因？模式修复基因将 利用观察到的胚胎所产下的 携带6个BCD基因拷贝的女性存活率降低。因此， 模式修复的阈值在四到六个副本之间 BCD基因。一种显性突变的基因筛查，这种突变会降低 携带四个BCD基因的雌性所产胚胎的存活率 已经启动，并将延长。将在以下位置分析PRS突变 分子和细胞水平。

Establishment of pattern is a major theme in developmental biology, whether it is studied at the molecular, cellular, or anatomical level. While a great deal of emphasis has been placed on applying the tools of molecular biology and genetics to the study of pattern emergence, the problem of maintenance and repair of pattern has been studied primarily from an anatomical viewpoint. Processes such as limb regeneration (in insects and amphibians) and imaginal disk repair (in insects) are examples of pattern repair. We propose the existence of embryonic Pattern repair system (Prs) genes that are responsible for the detection and the repair of pattern errors during Drosophila melanogaster embryogenesis. We have begun isolating and analyzing mutations that effect embryonic pattern repair. Embryonic pattern repair is observed in experiments where the dosage of the maternal effect gene, bicoid (bcd), is modulated. During oogenesis, bcd mRNA is anchored at the anterior end of the oocyte. Translation of bcd message upon fertilization results in a concentration gradient of BCD protein, which in turn triggers a cascade of transcriptional events that result in the specification of anterior structures (duplication of posterior structures is observed in the absence of BCD activity). Decreasing or increasing the bcd gene dosage from one to four copies, two copies is the normal complement, causes a number of anterior morphological markers to be shifted anteriorly or posteriorly, respectively. One would expect a corresponding size decrease or increase in larval anterior structures or possibly a reduction of viability. Unexpectedly, both of these embryo types develop to produce 'normal' larvae with viability and fertility equal to wild-type. These observations indicate that the embryo has the capacity to compensate for the pattern perturbations caused by changes in the BCD gradient. It is this compensatory response we are attributing to the pattern repair system. When and how does the pattern repair occur? In order to understand how the embryo responds to a pattern defect, one must have a detailed fate map of the affected area that includes information about cellular migration, shape, mitosis, and death. We have developed tools for selectively marking individual cells in live embryos and following their behavior through development. In addition, we and others have developed protocols for monitoring cell death in live embryos. With such a detailed fate map for wild-type embryos, we will be able to determine the changes in cellular behavior during the pattern repair process. What are the genes involved in pattern repair? Pattern repair genes will be identified by taking advantage of the observation that embryos laid by females with six copies of the bcd gene have reduced viability. Therefore, there is a threshold for pattern repair between four and six copies of the bcd gene. A genetic screen for dominant mutations that decrease the viability of embryos that laid by females with four copies of the bcd gene has been initiated and will be extended. Prs mutations will be analyzed at the molecular and cellular levels.