Anterior-Posterior Polarity of the Drosophila Embryo

果蝇胚胎的前后极性

• 批准号: 7011059
• 负责人: DONALD MORISATO
• 金额: $ 21.12万
• 依托单位: EVERGREEN STATE COLLEGE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7011059
• 关键词: Drosophilidae; arthropod genetics; biological signal transduction; developmental genetics; egg /ovum; embryogenesis; epithelium; gene expression; genetic models; genetic screening; invertebrate embryology; laboratory rabbit; molecular probes; nucleic acid sequence; oogenesis; ovary

DESCRIPTION (provided by applicant): Many basic insights into the mechanisms of human disease and development have come from experiments using Drosophila as a model system. Patterning of the Drosophila egg begins in the ovarian egg chamber. The gurken-Egfr signaling pathway is required to successively define the anterior-posterior and dorsal-ventral axes. During early oogenesis, Gurken in the oocyte activates Egfr in adjacent terminal follicle cells to specify a posterior fate. This oocyte-to-follicle cell signaling by Gurken is followed by an unidentified signal back to the oocyte from the posterior follicle cells, which causes reorganization of the microtubule organizing center. This signaling results in the localization of the maternal bicoid and oskar transcripts to opposite poles of the oocyte to define anterior-posterior asymmetry. Proper anterior-posterior axis formation requires the fettucine (fet) gene, which encodes an HMG box transcription factor. Embryos produced by mutant fet females develop with a bicaudal phenotype, in which the anterior is replaced by a mirror-image duplication of the posterior. Mosaic analysis indicates that fet\s required in the follicle cells. Yet, preliminary results indicate that bicoid and oskar mRNA are properly localized within the oocyte, arguing that fet is not involved in regulating the signal controlling microtubule polarity. Together, these observations suggest the existence of a novel follicle cell-to-oocyte signal that is hypothesized to regulate translation of oskar mRNA in the posterior. The overall objective of this proposal is to understand how fet action in follicle cells helps establish anterior-posterior polarity of the embryo. The DNA sequences encoding fet function will be defined, and the spatial expression of fet transcripts and Fet protein within the follicular epithelium will be investigated. The oocyte in mutant egg chambers will be further characterized with molecular probes; specific models that hypothesize fet involvement in the translational regulation of oskar mRNA will be tested. Finally, genetic screens aimed at identifying other components of the hypothesized signaling pathway will be carried out. An enduring problem in biology is understanding how an egg generates pattern along its body axes. The proposed experiments are aimed at characterizing how a particular gene called fettucine, which is conserved in humans, controls proper head-to-tail development in the fruit fly egg.

描述（由申请人提供）：对人类疾病和发育机制的许多基本见解都来自使用果蝇作为模型系统的实验。果蝇卵的图案化始于卵巢卵室。 gurken-Egfr 信号通路需要连续定义前后轴和背腹轴。在早期卵子发生过程中，卵母细胞中的 Gurken 会激活邻近终末卵泡细胞中的 Egfr，以指定后续命运。 Gurken 的卵母细胞到卵泡细胞信号传导之后，有一个未识别的信号从后卵泡细胞返回到卵母细胞，从而导致微管组织中心的重组。该信号传导导致母体 bicoid 和 oskar 转录物定位到卵母细胞的相反两极，从而定义前后不对称性。正确的前后轴形成需要宽面条 (fet) 基因，该基因编码 HMG 盒转录因子。突变fet雌性产生的胚胎发育为双尾表型，其中前部被后部的镜像复制所取代。镶嵌分析表明毛囊细胞需要 FET。然而，初步结果表明，bicoid 和 oskar mRNA 正确定位于卵母细胞内，认为 fet 不参与调节控制微管极性的信号。总之，这些观察结果表明存在一种新的卵泡细胞到卵母细胞信号，推测该信号可以调节后部 oskar mRNA 的翻译。该提案的总体目标是了解卵泡细胞中 fet 的作用如何帮助建立胚胎的前后极性。将定义编码 fet 功能的 DNA 序列，并研究 fet 转录本和 Fet 蛋白在滤泡上皮内的空间表达。突变卵室中的卵母细胞将通过分子探针进一步表征；将测试假设 fet 参与 oskar mRNA 翻译调节的特定模型。最后，将进行旨在识别假设的信号通路的其他组成部分的遗传筛选。生物学中一个持久的问题是了解卵子如何沿着其身体轴线产生图案。拟议的实验旨在表征人类保守的一种名为宽面条的特殊基因如何控制果蝇卵从头到尾的正常发育。