Control of collective cell movement by planar cell polarity signaling

摘要 称为会聚延伸（CE）的集体细胞运动驱动组织和器官的伸长， 基本上所有的动物。在脊椎动物中，CE由平面细胞极性（PCP）信号系统控制， PCP依赖性会聚延伸的缺陷与人类神经管缺陷和骨骼肌缺陷有关。 发育不良我们认为，严重缺乏有关CE的基本细胞生物学信息，因为它发生在 脊椎动物的体内研究是目前该领域的主要挑战。基于我们最近 在先进的成像和蛋白质组学的成功，这项建议采取了“细胞生物学”的方法，重点是 钙粘蛋白粘附、肌动蛋白组装和隔蛋白细胞骨架的基本细胞机器，以及如何 它们用于驱动PCP介导的CE。

Abstract Collective cell movements termed convergent extension (CE) drive the elongation of tissues and organs in essentially all animals. In vertebrates, CE is controlled by the planar cell polarity (PCP) signaling system, and defects in PCP-dependent convergent extension are associated with human neural tube defects and skeletal dysplasias. We feel that the profound lack of information regarding the basic cell biology of CE as it occurs in vertebrate animals in vivo represents the key challenge in the field at this time. Building on our recent successes in advanced imaging and proteomics, this proposal takes a "cell biological" approach, focusing on fundamental cellular machines of cadherin adhesion, actin assembly, and the septin cytoskeleton and how they are deployed to drive PCP-mediated CE.