Lipid biosynthesis and the control of morphogenesis

在胚胎发育的神经系统中，细胞增殖，获得特定细胞类型的特性，并相互形成细小的神经纤维连接。所有这些事件都需要磷脂的从头产生--这些是新膜的构建块，它们也被细胞转化为擅长携带发育中细胞接收的指令的分子(例如。增殖，表达该细胞类型特有的蛋白质，生长神经纤维)。我们对磷脂的精心调控如何控制神经系统发育的事件知之甚少，磷脂的产生既包括磷脂的产生，也包括在细胞中何时何地产生磷脂。有趣的是，我们发现一个酶家族，甘油-3-磷酸酰基转移酶(GPATs)，在神经系统的发育中优先表达--神经系统是一个与细胞运动有关的独特负担的组织。成为眼睛的组织中的透视眼细胞必须广泛移动，最终形成包围晶状体的一块薄薄的视网膜组织。这些运动可能需要一套独特的磷脂来组成运动细胞的膜，并需要一组补充的脂质信号分子来阅读“运动”指令。此外，一旦到达最终的视网膜位置，细胞，如捕捉光的光感受器和信息传输器，输出神经元，视网膜神经节细胞，也经历了其膜结构的广泛发展，以获得独特的形态，使它们能够执行其特定的功能。因此，我们有一个很好的眼睛和视网膜细胞模型，在这个模型中，我们可以开始破译调节和图案化的磷脂生物合成对胚胎细胞运动的重要性。我们使用非洲爪蛙的眼睛发育作为我们的模型，因为它们的视觉系统发展迅速，基因操作的简单方法是可用的，并且基本的分子机制在物种之间是保守的。

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.