Probing the elusive molecular mechanisms underlying vertebrate planar cell polarity

探索脊椎动物平面细胞极性背后难以捉摸的分子机制

• 批准号: RGPIN-2018-04960
• 负责人: Ciruna, Brian
• 金额: $ 2.33万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=647755
• 关键词: Probing; elusive; molecular; mechanisms; underlying

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.

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，并被积极地重新塑造成一个可识别的“成人”身体计划。这种显著的转变涉及细胞形状、图案和运动的无数变化(统称为细胞极性)，最终组装出器官、面部和四肢等复杂结构。这些事件中的任何一个微小的变化都会极大地改变正常的形态和器官功能。在下面的提案中，我们使用一个优雅的实验模型系统-斑马鱼-来了解在胚胎发育过程中，细胞极性是如何在分子和遗传水平上被控制的。斑马鱼的胚胎发育与哺乳动物的胚胎发育非常相似。然而，斑马鱼胚胎丰富、透明，很容易在显微镜下生长，我们已经建立了强大的技术来(实时)实际成像整个发育过程中细胞结构和运动的微观变化。此外，斑马鱼非常适合于遗传学研究，我们可以有选择地和系统地操纵基因功能，在不同的时空点上，研究它们对发育过程的影响。在这里，我们使用细胞生物学、胚胎学和斑马鱼的经典遗传学方法来确定在胚胎模式和形态发生过程中细胞极性是如何复杂地控制的。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，并识别新的分子和细胞生物学机制，这些机制在塑造脊椎动物胚胎的复杂发育事件的过程中，协调外部模式线索与细胞结构和运动。