An essential aspect of nervous system development is the extension by nerve cells (neurons) of long processes, called axons, which enable the neurons to communicate with each other or with muscles. In studies with a simple animal model for development, the nematode worm C. elegans, Dr. Finger's laboratory previously demonstrated that a family of proteins found in all animals, called septins, are important for extension of these processes. Worms are ideal for studying basic, conserved functions of septins that are likely to occur in the nervous systems of all animals, as there are only two worm septin genes, the fewest found in any organism. Dr. Finger's hypothesis is that septins influence whether actin, a component of the neuronal cytoskeleton crucial for axon extension, forms branched filaments, rather than linear bundles. The proposed project will employ approaches from genetics, cellular and developmental biology to identify the key proteins that allow septins to regulate actin branching in developing axons, and will determine how these proteins and septins work together to promote normal nervous system development. Notably, experiments using cultured neurons isolated from worm embryos will combine the powerful tools available for manipulation of C. elegans genes, with approaches not traditionally used in worm neurobiology. These studies will provide insights how nerve cell processes grow, enabling them to make the proper connections during embryonic development, and will expand the tools available for cell biological analysis of C. elegans neurons. Additionally, the career of Dr. Finger, a new investigator, will be fostered, while she provides training in research at the intersection of cell and developmental biology, genetics, and neuroscience for several undergraduate students, including women and minorities. The proposed research will be disseminated through peer-reviewed publications, conference presentations, and outreach to female high school students.
