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 in this guidance can have disastrous effects on the wiring of our nervous system, such as mental retardation, autism and schizophrenia. 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 a protein called Netrin, in connecting "motor neurons" in the spinal cord to their muscle targets in the limb. We have preliminary data that show that Netrin is important for this process and here, I propose experiments that will make us understand how Netrin binding to growing axons is translated into a signal that tells the axon which way to turn, grow out more, or stop growing. We know that such signals are also playing important roles in preventing broken axons from re-connecting, for example following spinal cord injury. Our findings will have important implications for our understanding of nervous system assembly in the embryo and the processes that prevent its re-assembly following injury.