Grant: Project Grant

During development nerve cells must form appropriate connections for the nervous system to function properly. A developing nerve cell extends a thin process called an axon that may grow past thousands of other cells before it reaches its target. We aim to identify the mechanisms that axons use to navigate in the embryo. Netrins are a family of proteins secreted by axonal targets during development. Without netrins, many types of axons become lost and the nervous system develops abnormally. Secreted proteins, like netrins, are thought to form gradients that direct axon growth in the early embryo. Our past findings and ongoing studies reveal gradients of netrin protein in the early embryo. In specific aim one, we address how these gradients are formed and maintained in the early embryo. The second aim proposes to investigate how cells read the distribution of netrin to move in a particular direction. This aim takes advantage of powerful new tools that we have developed to study neurons through collaborations with laboratories in the departments of Physics and Biomedical Engineering. We propose to use these tools to identify how a gradient of netrin causes molecular changes in the axon and how this results in directed axon growth. These studies will provide insight into fundamental mechanisms that regulate cell movement in the embryo. Importantly, mutations in netrins and netrin receptors are associated with developmental disorders in humans, and these proteins are also present in the mature nervous system. Obtaining a better understanding of how the nervous system develops is critical to generate strategies that aim to recover nervous system function that has been lost due to injury, aging, or neurodegenerative disease.