Functional assembly of an adult motor circuit in Drosophila

About This Grant

Project Summary The long term goal of this project is to characterize the molecular steps that allow a post-mitotic neuron to correctly integrate into a neural circuit, with both upstream and downstream targets. For this project, the primary focus is the development of a subset of the motor neurons that target the adult leg muscles in Drosophila melanogaster. Previous work established much of the ground-work on this system that will be built upon here. In particular, the specific neuroblast stem cells, their motor neuron progeny and birthdates, and all single neuron morphologies are known from previous work. A handful of key cell surface molecules of the immunoglobulin superfamily (IgSF) have been identified and characterized in detail in single motor neurons. These proteins are essential for some, but not all, motor neurons to make the correct connections. Finally, single cell RNA sequencing of motor neurons has identified additional cell surface proteins that also potentially contribute to target recognition and synapse formation. Building on these advances, we will use a powerful tool that was developed by us in collaboration with a computational biologist. This tool leverages both single cell RNA sequencing data with the known electron micrograph ‘connectome’ to predict molecules that interact across synapses. A second tool allows the visualization of cell surface proteins in vivo, in both in fixed and in live tissues. Together, these approaches will help to reveal how post-mitotic motor neurons establish their specific morphologies and connections with both upstream neurons and target muscles. Importantly, the principles and tools developed here will be broadly applicable to many problems currently being studied by both the development and neuroscience communities.