Grant: Operating Grant

What guides a nerve cell within a brain to choose a specific partner to connect with during neural circuit formation? Our research will investigate how the neural receptor Dscam (Down Syndrome Cell Adhesion Molecule) is involved in synaptic targeting decisions. We will use molecular genetics and imaging in the model organism, Drosophila, to characterize how cell-surface molecules influence synapse targeting decisions and synaptic connectivity. We make use of a genetically-specified, hard-wired sensory circuit involved in touch perception. We will analyze how disruption in Dscam's function produces synaptic targeting errors that affect the animal's behavior. These experiments will help uncover basic molecular and cellular mechanisms used by nervous systems to wire up pre-specified circuits. Furthermore, the gene for human Dscam lies within Chromosome 21, at a locus called the Down Syndrome Critical Region. Down syndrome is caused by a triplication of human Chromosome 21, and our experiments will also investigate how triplication of the Down Syndrome Cell Adhesion Molecule gene impairs synaptic targeting. Our research will help us understand first, how nervous systems develop normally and second, how dysfunction of specific molecules can cause abnormal development. We hope that by uncovering these molecular underpinnings we will be able to apply these findings to other brain diseases related to neural circuit miswiring.