Lipid biosynthesis and the control of morphogenesis

脂质生物合成和形态发生的控制

• 批准号: 238393-2012
• 负责人: McFarlane, Sarah
• 金额: $ 2.91万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629135
• 关键词: Lipid; biosynthesis; control; morphogenesis

In the developing nervous system of an embryo, cells proliferate, acquire cell type specific properties, and form thin nerve fiber connections with one another. All these events require the de novo production of phospholipids - these are the building blocks of new membrane, and they are also converted by the cells to molecules that are expert at carrying the instructions developing cells receive (eg. proliferate, express a protein unique to that cell type, grow a nerve fiber). We know little about how the carefully regulated production of phospholipids, both in terms of which phosphlipids get made and where and when in the cell they get made, may control the events of nervous system development. Interestingly, we find that a family of enzymes, the glycerol-3-phosphate acyltransferases (GPATs), are expressed preferentially in developing eyes of the nervous system - a tissue that has a unique burden with regards cell movement. Perspective eye cells in the sheet of tissue that becomes eye have to move extensively, ultimately making a thin block of retinal tissue that surrounds the lens. These movements likely require a unique set of phospholipids to make up the membranes of the moving cells, and a complement of lipid signaling molecules to read the "moving" instructions. Further, once in their final retinal location, cells such as the light-capturing photoreceptors, and the information relay output neurons, the retinal ganglion cells, also undergo extensive development of their membrane structures to acquire a unique morphology that allows them to carry out their specific functions. Thus, we have an excellent model with the eye and retinal cells in which we can start to decipher the importance of regulated and patterned phospholipid biosynthesis on cellular movement in the embryo. We use as our model the development of the eyes in the frog, Xenopus laevis, because their visual system develops rapidly, simple methods for gene manipulation are available, and basic molecular mechanisms are conserved across species.

在胚胎发育中的神经系统中，细胞增殖，获得特定类型的细胞特性，并形成彼此连接的细神经纤维。所有这些过程都需要磷脂的重新生成——这些磷脂是新膜的组成部分，它们也被细胞转化为分子，这些分子擅长携带发育中的细胞接收到的指令。增殖，表达这种细胞类型特有的蛋白质，长出神经纤维)。我们对精心调节磷脂的生产知之甚少，无论是磷脂是如何产生的，还是在细胞中何时何地产生的，都可能控制神经系统发育的事件。有趣的是，我们发现一个酶家族，甘油-3-磷酸酰基转移酶（GPATs），在神经系统发育中的眼睛中优先表达，这是一个对细胞运动有独特负担的组织。形成眼睛的组织薄片中的透视眼细胞必须广泛移动，最终形成包围晶状体的薄视网膜组织块。这些运动可能需要一组独特的磷脂来构成运动细胞的膜，并需要一组脂质信号分子来读取“运动”指令。此外，一旦进入视网膜的最终位置，诸如光捕获感受器、信息传递输出神经元、视网膜神经节细胞等细胞也会经历其膜结构的广泛发育，以获得独特的形态，从而使它们能够执行特定的功能。因此，我们有了一个极好的眼睛和视网膜细胞模型，在这个模型中，我们可以开始破译受调节和有模式的磷脂生物合成对胚胎细胞运动的重要性。我们以非洲爪蟾（Xenopus laevis）的眼睛发育为模型，因为它们的视觉系统发育迅速，有简单的基因操作方法，而且基本的分子机制在物种间是保守的。