About Our Lab

Research in our lab

Our lab studies how animal nervous systems are wired during embryonic development. Our main focus is on axon guidance, the process by which neuronal axons are guided through the developing nervous system to form functional connections with other neurons and non-neural cells. We examine the basic mechanisms of axon guidance using classical and modern genetic approaches in the fruit fly Drosophila melanogaster, and we use a comparative approach within and between species to examine the functional diversity of axon guidance pathways in modern animals, and to reconstruct the evolution of axon guidance mechanisms in animal lineages. Current research in the lab addresses the following topics:

Genetic regulation of axon guidance decisions

ResearchThe basic patterns of connectivity in animal nervous systems are hard-wired: the expression and activity of specific genes determines each neuron’s identity and its axon and dendrite morphology. As each migrating axon encounters a series of choice points, its pattern of gene expression specifies its response to extracellular cues and ultimately guides it to its final synaptic target. We use Drosophila as a model to study how axon guidance receptors and their associated ligands contribute to specific guidance decisions. Using genetic labeling techniques, we examine the behavior of defined subsets of axons in embryos where individual gene activities are increased, decreased, or otherwise modified. This approach allows us to dissect the genetic regulation of specific axon guidance decisions with a high degree of precision.

Functional diversity of axon guidance receptor families

researchAxon guidance receptors expressed on the growth cone surface allow pathfinding axons to respond to extracellular cues as they grow towards their synaptic targets. In some cases, related receptors can specify distinct guidance outcomes in response to the same ligand. How this functional diversity is achieved is not well understood. In Drosophila, the three members of the Roundabout (Robo) receptor family share a single ligand (Slit), yet specify distinct, and in some cases opposing, axon guidance outcomes. We use gene-replacement and structure-function approaches to examine the functional diversity of Robo receptors in Drosophila. These studies will help us understand how a limited number of genes can specify the complex pattern of neuronal connectivity found in modern animals.

Structure-function studies of axon guidance receptors

ResearchMany axon guidance receptors are multifunctional proteins, and can specify distinct guidance outcomes in different contexts. We use structure-function studies to dissect the functional contribution of individual domains within axon guidance receptors. We have found that distinct axon guidance activities in Robo family receptors are genetically separable, and we can selectively add, delete, or exchange guidance activities between related receptors using molecular approaches. We hope to connect these molecular insights to cellular mechanisms to explain how related receptors can specify distinct developmental outcomes.

Evolution of axon guidance mechanisms

researchThe mechanisms regulating axon guidance have undergone substantial evolutionary change in animal lineages, as components of conserved genetic pathways have undergone gene duplication and functional divergence, yet much of the existing research into neural developmental mechanisms in insects has focused on the fruit fly Drosophila. We are developing the flour beetle Tribolium castaneum as a second genetic model insect for the study of axon guidance. We investigate the function of axon guidance genes in Tribolium through RNAi-mediated knockdown, and use gene replacement techniques in Drosophila to examine the conservation of function between fly and beetle orthologs of molecules like Slit and its Robo receptors. By comparing axon guidance in Drosophila and Tribolium, we hope to gain a broader perspective on neural development in insects, and address the question of how axon guidance mechanisms have changed over evolutionary time.