The regulation of early embryo cleavage by cell polarity proteins

基因组测序已经确定了制造动物所需的蛋白质。然而，我们才刚刚开始了解这些蛋白质如何共同作用来构建动物组织。人体中最常见的组织是构成我们皮肤和器官的细胞片。蛋白质是如何组织这些薄片形成皮肤、肺、心脏或胃的？我的实验室正在使用果蝇作为一个简单、易处理的模型系统来解决这个基本问题。我们可以使用果蝇中可用的强大基因技术来扰乱蛋白质功能，并识别对组织发育重要的蛋白质。我们将这些操作与先进的成像技术结合起来，以监测动物胚胎发育过程中的分子定位、细胞形状和相互作用以及组织结构。通过这种方式，我们正在发现指导动物发育组织结构特定变化的蛋白质和分子网络。通过将一组蛋白质与特定的组织变化联系起来，组织变化的分子基础将被确定，从而基因组和整个动物之间的联系将变得清晰。同样的蛋白质和细胞过程也是动物组织发育的基础。因此，我们对具有实验优势的果蝇胚胎的研究对于了解人类组织是如何正常形成的，以及了解它们在癌症等疾病中是如何分解的很重要。它也与组织和器官的工程学有关。*这项建议侧重于如何通过早期胚胎分裂(细胞分裂)产生发育中的动物的第一个组织。在分子和细胞水平上，我们正在追寻在细胞中形成空间标志的蛋白质(极性蛋白质；激酶PAR-1和aPKC)如何调节电缆和马达网络(肌动蛋白细胞骨架网络)的位置和收缩，以便在正确的位置分割细胞，并通过多轮快速分裂继续这样做。我们正在研究保守的蛋白质，并利用果蝇早期发育的独特方面来确定在其他模型系统中可能无法检测到的细胞分裂调节机制。我们的研究应该普遍适用于动物之间的细胞分裂。

Genome sequencing has identified the proteins required for making an animal. However, we are just beginning to understand how these proteins function together to build animal tissues. The most common tissues in the body are the sheets of cells that form our skin and organs. How do proteins organize these sheets to form the skin, lungs, heart or stomach? My lab is addressing this fundamental question using the fruit fly as a simple, tractable model system. We can use the powerful genetic techniques available in the fruit fly to disrupt protein function and to identify proteins important for tissue development. We couple these manipulations with advanced imaging techniques to monitor molecular positioning, cell shapes and interactions, and tissue organization as an animal embryo develops. In this way, we are discovering the proteins and molecular networks that direct specific changes in tissue structure for animal development. By linking sets of proteins to specific tissue changes, the molecular bases of tissue changes will be defined, and thus the links between the genome and the whole animal will become clear. The same proteins and cellular processes underlie tissue development across animals. Thus, our research in the experimentally advantageous fruit fly embryo is important for understanding how human tissues form normally, and for understanding how they break down in diseases like cancer. It is also relevant to the engineering of tissues and organs.****This proposal focuses on how the first tissue of a developing animal is generated through early embryo cleavage (cell division). At the molecular and cellular level, we are pursuing how proteins that form spatial landmarks in the cell (polarity proteins; the kinases Par-1 and aPKC) regulate the positioning and contractility of networks of cables and motors (actomyosin cytoskeleton networks) to divide the cell at the correct location, and to continue doing so with many rounds of rapid division. We are studying conserved proteins and taking advantage of unique aspects of early fruit fly development to identify cell division regulatory mechanisms that may have eluded detection in other model systems. Our research should be generally relevant to cell division across animals.********