Departamento de Genética, Facultad de CC Biológicas, Universidad de Valencia, Burjassot 46100, Valencia, Spain.
Curr Genomics. 2012 Dec;13(8):609-22. doi: 10.2174/138920212803759721.
Collective and directed cell movements are crucial for diverse developmental processes in the animal kingdom, but they are also involved in wound repair and disease. During these processes groups of cells are oriented within the tissue plane, which is referred to as planar cell polarity (PCP). This requires a tight regulation that is in part conducted by the PCP pathway. Although this pathway was initially characterized in flies, subsequent studies in vertebrates revealed a set of conserved core factors but also effector molecules and signal modulators, which build the fundamental PCP machinery. The PCP pathway in Drosophila regulates several developmental processes involving collective cell movements such as border cell migration during oogenesis, ommatidial rotation during eye development, and embryonic dorsal closure. During vertebrate embryogenesis, PCP signaling also controls collective and directed cell movements including convergent extension during gastrulation, neural tube closure, neural crest cell migration, or heart morphogenesis. Similarly, PCP signaling is linked to processes such as wound repair, and cancer invasion and metastasis in adults. As a consequence, disruption of PCP signaling leads to pathological conditions. In this review, we will summarize recent findings about the role of PCP signaling in collective cell movements in flies and vertebrates. In addition, we will focus on how studies in Drosophila have been relevant to our understanding of the PCP molecular machinery and will describe several developmental defects and human disorders in which PCP signaling is compromised. Therefore, new discoveries about the contribution of this pathway to collective cell movements could provide new potential diagnostic and therapeutic targets for these disorders.
细胞的集体和定向运动对于动物界中各种发育过程至关重要,但它们也参与伤口修复和疾病。在这些过程中,细胞群在组织平面内定向,这被称为平面细胞极性(PCP)。这需要进行严格的调控,部分通过 PCP 途径进行。虽然该途径最初在果蝇中进行了表征,但随后在脊椎动物中的研究揭示了一组保守的核心因子,以及效应分子和信号调节剂,它们构成了基本的 PCP 机制。果蝇中的 PCP 途径调节几种涉及集体细胞运动的发育过程,例如卵发生过程中的边缘细胞迁移、眼睛发育过程中的小眼旋转以及胚胎背侧闭合。在脊椎动物胚胎发生过程中,PCP 信号也控制集体和定向细胞运动,包括原肠胚形成过程中的会聚延伸、神经管闭合、神经嵴细胞迁移或心脏形态发生。同样,PCP 信号与伤口修复和成人中的癌症侵袭和转移等过程有关。因此,PCP 信号的破坏会导致病理状况。在这篇综述中,我们将总结最近关于 PCP 信号在果蝇和脊椎动物中的集体细胞运动中的作用的发现。此外,我们将重点介绍果蝇中的研究如何与我们对 PCP 分子机制的理解相关,并描述几种 PCP 信号受损的发育缺陷和人类疾病。因此,对该途径对集体细胞运动的贡献的新发现可能为这些疾病提供新的潜在诊断和治疗靶点。