Probing the elusive molecular mechanisms underlying vertebrate planar cell polarity

在脊椎动物胚胎发育过程中，一个不起眼的细胞球迅速增殖、生长，并被积极地重塑成一个可识别的“成人”身体计划。这种显著的转变涉及细胞形状、模式和运动（统称为“细胞极性”）的无数变化，最终组装出复杂的结构，如器官、面部和四肢。这些事件的任何轻微变化都可能极大地改变正常的形态和器官功能。******在下面的建议中，我们使用一个优雅的实验模型系统-斑马鱼-来了解细胞极性是如何在分子和遗传水平上控制的，在胚胎发育的过程中。斑马鱼的胚胎发生与哺乳动物非常相似。然而，斑马鱼的胚胎是丰富的，透明的，很容易在显微镜下生长，我们已经建立了强大的技术来实际成像（实时）细胞结构和运动在整个发育过程中发生的微观变化。此外，斑马鱼非常适合基因研究，我们可以在不同的空间和时间点有选择地和系统地操纵基因功能，以研究它们对发育过程的影响。******在这里，我们采用细胞生物学，胚胎学和斑马鱼的经典遗传方法来确定细胞极性是如何在胚胎模式和形态发生过程中受到复杂控制的。拟议的研究具有巨大的潜力，可以扩大我们对器官发育的理解，并确定新的分子和细胞生物学机制，这些机制可以协调外部模式线索与形成脊椎动物胚胎的复杂发育事件过程中的细胞结构和运动。

During vertebrate embryonic development, an unassuming ball of cells rapidly proliferates, grows, and is actively re-modeled into a recognizable ‘adult' body plan. This remarkable transformation involves countless changes in cell shape, pattern and movement, (collectively referred to as “cell polarity”), which ultimately assemble complex structures like organs, faces and limbs. Slight changes to any of these events can dramatically alter normal form and organ function.******In the following proposal, we use an elegant experimental model system – the zebrafish – to understand how cell polarity is controlled at a molecular and genetic level, over the course of embryonic development. Zebrafish embryogenesis is remarkably similar to that of mammals. However, zebrafish embryos are abundant, transparent, easily grown under a microscope, and we have established powerful techniques to actually image (in real time) the microscopic changes in cell structure and movement that occur throughout development. Furthermore, zebrafish are well suited for genetic studies, and we can selectively and systematically manipulate gene function, at different points in space and time, to study their effects on developmental processes. ******Here, we employ cell biology, embryology, and classic genetic approaches in zebrafish to determine how cell polarity is intricately controlled during embryonic patterning and morphogenesis. Proposed research holds tremendous potential to expand our understanding of organ development, and to identify novel molecular and cell biological mechanisms that co-ordinate extrinsic patterning cues with cell structure and movement over the course of complex developmental events that shape the vertebrate embryo.