Asymmetric cell division in the C elegans embryo

描述(申请人提供)：不对称细胞分裂是包括人类在内的各种动物发育过程中的一个基本过程。我们的干细胞必须经历反复的不对称细胞分裂，才能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进行不对称分配。我们正在使用线虫秀丽线虫作为模型来研究细胞的不对称分裂。在线虫的第一次细胞分裂之前，P颗粒(对生殖系发育至关重要的核糖核蛋白复合体)和其他几种蛋白质和mRNA变得不对称地定位在受精卵的一端或另一端。同时，以肌动蛋白为基础的皮质和中央细胞质的极化流动也发生了。后来，在有丝分裂期间，有丝分裂的纺锤体移动到不对称的位置。结果是不同大小的子细胞含有不同的分子成分。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的问题的极佳模型。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)研究线虫受精卵中有丝分裂纺锤体不对称定位的机制，以及(3)克隆和鉴定P颗粒和有丝分裂纺锤体定位所需的新基因。我们预计我们将了解到关于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.