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The overall goal of this work is to elucidate developmental and molecular mechanisms that lead to the production of a functional central nervous system (CNS). For many animals the CNS is the most intricate and complex organ in the body. As the CNS forms, not only must the various types of neurons and glia take on their identities, but once generated, these cells must send out a large number of processes and establish very precise connections on a diverse array of target tissues. For all of these steps to occur normally to produce a functioning nervous system, the appropriate genes must be regulated in a precise temporal and spatial fashion within CNS cells. Our research uses Drosophila melanogaster as a model system, and it focuses on a unique set of cells within the Drosophila CNS, the midline cells. These cells separate the two symmetrical halves of the CNS and provide many signals that guide axon growth of developing neurons. Our objectives and experiments are designed to understand the functions of genes required for specific midline cells to differentiate into glia and not neurons. These experiments focus on the role of three genes (single-minded, Dichaete and Sox Neuro) found in the midline at different stages of development. Our approach is to examine the role of these three genes during midline glial formation, using mutational and overexpression analyses. This research will impact our knowledge of critical developmental events of neurons and glia, which is necessary to fully understand the prerequisites of their ultimate behavior and function. For example, a current challenge in medicine is to regenerate neurons in damaged tissue. Presently, even in cases in which neurons can be introduced or regenerated, it is difficult to predict their precise behavior. The identification and understanding of neural and glial specification molecules in this model system, as well as axonal pathfinding molecules and their functions, will lead to the ability to control the behavior of neurons. This research will contribute to our knowledge of basic processes of gene expression, cell signaling, cell connectivity and signal transduction, and it will ultimately lead to new ideas and techniques for treating neuronal birth defects and lesions. This work will provide research and mentoring opportunities to both traditional and underrepresented undergraduate and graduate students. It will offer students scientific training in genetics and molecular, cellular, and developmental biology that will enhance their education and prepare them for careers in the life sciences. In addition, talented high school students have been involved in several components of this project, and this training will continue. The Drosophila CNS is an excellent model for training students in nervous system development and function, and we exploit our experimental system in a course in Developmental Genetics for upper level undergraduate students.
