Research

Developmental axon pruning of mushroom body (MB) γ neurons in the Drosophila fruit fly is a perfect model system to study neuronal remodeling: Not only can we harness the awesome genetic power of the fly and its short life cycle but we can also view the stereotypical neuronal remodeling as they occur in vivo during the larva to adult metamorphosis (see Figure 1). In our lab we use genetic tools to explore the roles of intracellular signaling, trafficking and cytoskeletal changes during neuronal remodeling. In addition, we employ genomic tools to characterize in high resolution the transcriptional landscape of γ neurons at different stages of development.

Following pruning, γ neurons undergo developmental axon regrowth. Recently, we have provided the first evidence that developmental axon regrowth is genetically regulated, distinct from initial axon outgrowth and shares similarities with axon regeneration following injury. By combining genetics and genomics, we aim to provide a deep mechanistic understanding of axon regrowth that should, in the long run, impinge on our understanding of the constraints of axon regeneration following injury.

Glia are important for clearing the axonal debris following pruning. However, the identity of these glia is not known. Additionally, the extent to which glia play an instructive VS permissive role during pruning is not well understood. We use state-of-the-art genetic tools to label and manipulate both glia and neurons in the same brain to uncover the important genes within glia that affect remodeling in the neurons.

A complex biological process occurring late in development, such as axon pruning, most likely utilizes molecules that are also required in a wide variety of other developmental processes. Mosaic analyses, which can be used to study such questions, have until recently not been very useful in studying the nervous system where a single mutant axon needs to be visualized in the background of thousands of non-clonal axons. To solve this problem, the Luo laboratory developed the MARCM technique, which enables the creation of homozygous mutant clones (which can be as small as single cells), which are positively labeled.