Project 1: MicroRNA Regulation of Synapse Development and Maintenance

Much has been learned about the signaling pathways and networks of proteins that function together to build and modulate synaptic connections.  This rich molecular landscape is under the control of multiple classes of regulatory factors.  MicroRNA (miR) are versatile posttranscriptional regulators capable of tuning levels of gene expression across a large number of target genes. Through genetic screens in Drosophila, we have discovered that synapse formation and growth are controlled by conserved microRNA genes that orchestrate different stages of synapse development through distinct sets of direct and indirect targets. Having recently created a means of selectively inhibiting the function of any microRNA with spatio-temporal precision in vivo, we are now equipped to survey the functions of all microRNAs in Drosophila in many aspects of neural development, connectivity, behavior, and neurodegeneration.  Once this regulatory landscape has been mapped through comprehensive screens in this model organism, it will be possible for us to test the conservation of these mechanisms in mammalian neurons and circuits.