Lipid biosynthesis and the control of morphogenesis

在胚胎发育的神经系统中，细胞增殖，获得细胞类型特异性，并相互形成细神经纤维连接。所有这些事件都需要从头产生磷脂-这些是新膜的构建模块，并且它们也被细胞转化为擅长携带发育细胞接收的指令的分子（例如。增殖、表达细胞类型特有蛋白质、生长神经纤维）。我们对磷脂的精心调控的生产知之甚少，无论是哪种磷脂，还是它们在细胞中何时何地产生，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，即甘油-3-磷酸酰基转移酶（GPAT），优先在神经系统的发育中的眼睛中表达-神经系统是一种在细胞运动方面具有独特负担的组织。透视眼的细胞在组织片，成为眼睛必须广泛地移动，最终使一个薄块视网膜组织包围透镜。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，一旦在它们的最终视网膜位置，诸如光捕获光感受器和信息中继输出神经元（视网膜神经节细胞）的细胞也经历它们的膜结构的广泛发育，以获得允许它们执行其特定功能的独特形态。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，我们可以开始破译胚胎细胞运动中受调控和模式化的磷脂生物合成的重要性。我们使用青蛙眼睛的发育作为模型，非洲爪蟾，因为它们的视觉系统发育迅速，基因操作的简单方法可用，并且基本的分子机制在物种间是保守的。

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.