During brain development, nerve cells must migrate considerable distances to reach their final locations before they can connect properly to other nerve cells. Although many different signals affect this process, the complexity of higher mammals has made it difficult to determine how specific proteins control cell movements within the brain. As an alternative strategy, simpler insect nervous systems can be used to model how particular types of proteins affect cell behavior, providing the framework for testing the role of related proteins in higher animals. This project will exploit the unique advantages of insect preparations to define the role of an important class of cell surface receptors called "Ig-CAMS", which are found in all nervous systems but whose functions are poorly understood. Time-lapse imaging and fluorescent labeling will be used to determine how different Ig-CAMs control distinct patterns of cell movement. A combination of molecular and biochemical methods will then be used to test the role of newly discovered "adapter" proteins that govern the effects of Ig-CAMs at specific times and places. The results of these studies will reveal new principles about how these protein classes function in more complex organisms, including the human brain.
This project will explore an important aspect of nerve cell guidance that plays a major role in controlling the formation of the brain. Because insect model systems are relatively inexpensive and easy to manipulate, the proposed studies will provide valuable training opportunities for students and educators from a variety of backgrounds, including undergraduates lacking prior research experience. This grant will also support ongoing efforts to encourage participation by women and underrepresented minorities in scientific discovery. The ultimate goal of this project will be improve current knowledge about the fundamental mechanisms that control cell migration in the developing nervous system.
