Control of collective cell movement by planar cell polarity signaling

摘要 被称为会聚延伸(CE)的集体细胞运动推动了组织和器官的伸长 基本上是所有的动物。在脊椎动物中，CE由平面细胞极性(PCP)信号系统控制，并且 PCP依赖的会聚延伸缺陷与人类神经管缺陷和骨骼相关 发育不良。我们认为，关于CE的基本细胞生物学信息的严重缺乏，因为它发生在 活体脊椎动物是目前该领域的关键挑战。在我们最近的基础上 在先进的成像和蛋白质组学方面的成功，这项建议采取了“细胞生物学”的方法，重点是 钙粘附素黏附、肌动蛋白组装和Septin细胞骨架的基本细胞机及其如何 它们被部署来推动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.