A Genetic Model for Dendritic Spine Development
Our laboratory is interested in how neuronal dendrite and axon morphologies are formed, sculpted, and finalized during development. Dendrites are the main site of synaptic input and integration in the nervous system and elucidating the molecular pathways governing dendrite development is critical to understanding how dendritic morphologies are affected by important events such as aging, disease, and learning.
We would like to discover which molecules are required for proper dendrite formation and how these molecules biochemically function and genetically interact to regulate dendrite morphology. Drosophila is an ideal model system to use to address this problem. We have developed a system using green fluorescent protein (GFP) in transgenic fruit flies to visualize neuronal dendrites in living embryos. Using this system we conducted a preliminary genetic screen and identified several genes required for dendrite development. These include kakapo, a cytoskeletal protein with homology to dystrophin; enabled, a substrate of the tyrosine kinase Abl; and flamingo, a seven-transmembrane encoding gene with homology to G-protein coupled receptors. We also identified Sequoia, a novel zinc finger protein identified in the screen that is expressed specifically in the nervous system.
Our lab also studies axon development as many genes first identified as playing a role in dendrite development, turn out to be required for axon development as well. Indeed, enabled, flamingo, kakapo, and sequoia all play roles in axon guidance/development. We will use the full gamut of molecular, biochemical and genetic techniques available and utilize the conservation of gene sequence and function between Drosophila and man to move to mammalian model systems when they prove more amenable to answering the questions at hand. Current projects include examining downstream targets of sequoia for possible roles in morphogenesis as well as identifying the protein complex containing kakapo which likely functions in linking external signaling pathways to the internal cytoskeleton.