Asymmetric cell division in the C elegans embryo

描述（由申请人提供）：不对称细胞分裂是包括人类在内的多种动物发育的重要过程。我们的干细胞必须经历反复的不对称细胞分化，以产生对我们的健康至关重要的细胞。拟议项目的长期目标是了解如何不对称地划分。我们正在使用线虫秀丽隐杆线虫作为模型来研究不对称细胞分裂。在C.线虫、P颗粒（生殖细胞发育所必需的核糖核蛋白复合物）和几种其他蛋白质和mRNA变得不对称地定位于受精卵的一端或另一端。同时，皮层和中央细胞质的肌动蛋白为基础的极化流发生。随后，在有丝分裂期间，有丝分裂纺锤体移动到不对称位置。其结果是包含不同分子成分的大小不等的子细胞。将遗传学与实时成像相结合的潜力使该系统成为解决细胞如何不对称分裂问题的绝佳模型。我们的具体目标是：（1）确定已知基因在P颗粒定位中的作用;（2）研究C.（3）克隆并鉴定了P颗粒和有丝分裂纺锤体定位所需的新基因。我们希望我们将了解有关细胞如何不对称分裂的重要新信息，这些信息将提出机制并指导包括人类在内的哺乳动物的研究。

DESCRIPTION (provided by applicant): Asymmetric cell division is an essential process in the development of diverse animals, including humans. Our stem cells must undergo repeated asymmetric cell disivions to produce ceils of critical importance to our health. The long-term objective of the proposed project is an understanding of how divide asymmetrically. We are using the nematode CaenorhabdiUs elegans as a model to study asymmetric cell division. Before the first cell division in C. elegans, P granules (ribonucleoprotein complexes that are essential for germline development) and several other proteins and mRNAs become asymmetrically localized to one end of the zygote or the other. Simultaneously, actin-based polarized flows of cortical and central cytoplasm occur. Later, during mitosis, the mitotic spindle moves to an asymmetric position. The result is unequal-sized daughter cells containing distinct molecular components. The potential for combining genetics with live imaging makes this system an excellent model for addressing questions about how cells divide asymmetrically. Our specific aims are to (1) determine how known genes function in the localization of P granules, (2) investigate the mechanism of asymmetric mitotic spindle positioning in the C. elegans zygote, and (3) clone and characterize a new gene required for both P granule and mitotic spindle positioning. We expect that we will learn important new information about how cells divide asymmetrically that will suggest mechanisms and guide studies in mammals, including humans.