Nuclear Migration and Early Zygotic Gene Action in Drosophila

本研究的具体目标是：1)利用新开发的免疫细胞化学技术，获得果蝇胚胎在卵裂发育阶段的细胞核和细胞骨架组织的详细图像。2)批判性地分析细胞骨架元件微管蛋白和肌动蛋白在分裂核进入外周时如何重组的确切细节。这些结果将通过诺马尔斯基DIC光学观察和视频技术记录的活胚胎的实时观察得到增强。这些结果与之前的工作相结合，将为分析许多已知的影响早期发育的果蝇突变提供描述性基础。(3)更详细地研究嵌入甚至跳过的基因的突变对早期发育的影响。这两个基因的突变对胚胎是致命的，并以可复制和空间特异性的方式破坏分割。该建议旨在进一步了解这些基因与胚胎中提供结构和运动的细胞骨架元件之间的关系，特别强调基于肌动蛋白和微管蛋白的细胞骨架。从长远来看，了解这些基因和其他基因如何构建果蝇的身体结构，应该会告诉我们类似的基因如何在包括人类在内的高等真核生物中起作用。卵子与精子的受精启动了一个发育程序，产生了一个完全可存活的成年动物。这个发育过程完全是由受精卵的内容物决定的，发育生物学家面临的挑战是，如何准确地破译卵子中存在的信息是如何首先储存起来的，然后随着胚胎的发育而被利用和处理。卡尔博士的工作将提供受精后最早事件的关键信息。

The specific goals of this proposal are: 1) To achieve, using newly developed immunocytochemical techniques, a detailed picture of both nuclear and cytoskeletal organizations present in Drosophila embryos during the cleavage stages of development. 2) To critically analyze the exact details of how the cytoskeletal elements tubulin and actin reorganize as the cleavage nuclei enter the periphery. These results will be augmented with real- time observations of living embryos viewed with Nomarski DIC optics and documented with video technology. These results, in conjunction with the previous work will provide the descriptive foundations for which many known Drosophila mutations affecting early development can be analyzed. 3) To examine in greater detail the effects mutations in the engrailed and even-skipped genes have on early development. Mutations in these two genes are lethal to the embryo, and disrupt segmentation in a reproducible and spatially specific manner. This proposal is designed to further our understanding of the relationship between these genes and cytoskeletal elements in the embryo that provide structure and movement, with special emphasis on the actin and tubulin-based cytoskeletons. In the long term, an understanding of how these and other genes act to build the body plan of Drosophila should tell us how similar genes work in higher eukaryotes including humans. %%% Fertilization of an egg by the sperm initiates a developmental program that results in a fully viable adult animal. This developmental program is completely specified by the contents of the fertilized egg, and the challenge facing developmental biologists is to decipher exactly how the information that is present in the egg is first stored, and then subsequently utilized and processed as the embryo develops. Dr. Karr's work will provide key information about the very earliest events following fertilization.