Lipid biosynthesis and the control of morphogenesis

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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.