John B. Thomas, Ph.D.

Research

The focus of our research is to understand how neurons are assembled during development to produce a functioning nervous system. The growth cones at the tips of developing axons are guided to their synaptic target cells by cues in the extracellular environment. Specific receptors on the growth cones recognize these cues and transduce signals that ultimately lead to changes in direction of growth. To identify these guidance molecules, we have taken a genetic approach in Drosophila by isolating mutations that alter specific features of axon guidance and target recognition. For our mutant screens we created a set of axon-targeted reporters that allow us to directly visualize the morphology of neurons expressing them. Our screens have yielded a number of molecules, from axon guidance receptors such as Derailed, which together with its ligand Wnt5, controls how axons project across the midline, to a family of transcription factors, the LIM-homeodomain proteins, which combinatorially control motor neuron pathway selection and muscle target recognition. The guidance molecules we have discovered in Drosophila have mammalian homologs that turn out also to function in axon guidance.

From the work of our lab and a number of others we know something about how axons are guided to their target destinations in order to eventually synapse with their appropriate target cells, thus forming the neural circuits that make up the nervous system. However, we have little understanding of how these circuits are actually assembled. We know even less about how they generate behaviors. To begin addressing these questions, we are functionally and anatomically defining neural circuits underlying “simple” behaviors such as locomotion. Our long-term goal is to understand how these circuits develop and function.