Cell polarity in C.elegans

这一建议涉及理解微管在早期秀丽隐杆线虫胚胎极性的建立和转导中的作用。秀丽隐杆线虫的第一次细胞分裂时，皮层分为两个结构域，由不同的PAR蛋白定义。这些PAR皮质结构域的形成被认为是由精子中心体的元素驱动的，并定义了胚胎的前后轴。随后，这些PAR蛋白通过调节细胞骨架的特性介导不对称细胞分裂的形成。在这些不对称事件中，突出的是不对称纺锤体的形成，导致两个不同大小的细胞。我们既不了解中心体/微管如何驱动皮质结构域的形成，也不了解这些皮质结构域如何调节微管的动力学来驱动不对称细胞分裂。在此，我们建议1)利用中心体突变体和激光消融来确定中心体成分在建立细胞极性中的作用2)开发技术来分析细胞不对称分裂过程中微管的变化动力学。我们将把这一分析与微管的激光消融结合起来，试图确定产生不对称细胞分裂所需的微管的力。

This proposal is concerned with understanding the role of microtubules in the establishment and transduction of polarity in the early C.elegans embryo. During the first cell division of C.elegans the cortex divides into two domains, defined by different PAR proteins. The formation of these PAR cortical domains is thought to be driven by elements of the sperm centrosome and defines the anterior-posterior axis of the embryo. Subsequently these PAR proteins mediate the formation of an asymmetric cell division, by modulating the properties of the cytoskeleton. Prominent among these asymmetric events is the formation of an asymmetric spindle, leading to two cells of different sizes. We understand neither how centrosomes/microtubules drive the formation of the cortical domains, nor how these cortical domains modulate the dynamics of the microtubules to drive asymmetric cell division. Here we propose 1) To use both mutants in centrosomes and laser ablation to define the role of centrosome components in establishing cell polarity 2) To develop techniques to analyze the changing dynamics of microtubules during asymmetric cell division. We will combine this analysis with laser ablation of microtubules in attempt to identify the force generating microtubules required for asymmetric cell division.