Grant: Operating Grant

The basic units of nervous systems are circuits formed by precisely interconnected neurons. Neurons connect by extending processes called "axons" that are guided to their targets over long distances. Loss of accuracy of this guidance can have disastrous effects on the wiring of our nervous system, including mental retardation and even death. Some studies have suggested that diseases such as autism and schizophrenia might be caused by inappropriate connections formed between specific regions of the brain. Knowing how our nervous system is wired is therefore extremely important if we want to understand how such diseases develop and what could be done to cure them. In this proposal I outline experiments that address the role of the axon guidance protein family called "Eph receptors". Specific Objectives: (1) Determine how Eph receptor function is modulated by proteins that bind to it. (2) Determine how Eph receptors relay their signals inside the neurons. (3) Determine how Eph receptors work together with other kinds of axon guidance receptors. Hypothesis. To achieve a greater variety of responses, the Eph receptor function is modified by interacting with other proteins. Methods: I will test this hypothesis by using the mouse and chick model systems. Both share similar spinal cord anatomy, and use very similar proteins in their development. The mouse has the advantage of the possibility of using animals with "knocked out" genes, but chick embryos are more accessible and can be manipulated while inside the egg.