The focus of the lab is the study of the molecular mechanisms that lead to the generation of specific neural circuits in the brain, which in turn subserve specific behaviors. We are interested in the developmental aspect of neural circuit generation as well as later aspects of maintenance and modification of neural circuits, which presumably are the basis of learning and memory processes. Due to the complexity of the vertebrate brain, we use the much simpler nervous system of the nematode C. elegans as a model system. We know the complete connectivity of every single neuron in C. elegans and single cell laser ablations have identified specific neural circuits required to execute specific behaviors. The completely sequenced genome of C. elegans as well as its amenability to classical genetic methods allow the identification of molecules that are required for the neural differentiation and the generation of specific neural circuits.
At the moment we have focused our interests on a specific class of transcription factors, the LIM homeobox genes. Seven of these genes exist in C. elegans and we have characterized 4 of these so far. All these genes are expressed in a restricted subset of postmitotic neurons in the brain; their maintained expression throughout adulthood suggest a role for these genes not only in the initial differentiation process but also in the maintenance of the differentiated state. Indeed, our molecular, genetic and behavioral analysis of several of these genes demonstrated their involvement in late neural differentiation processes. Two of these genes, ttx-3 and lin-11 are required to specify the function of two interneurons in a neural circuit that subserves a learning and memory paradigm in C. elegans, the thermosensory neural circuit. Another gene, lim-6 is required for the rhythmic execution of a motor program and is presumably also involved in sensory neural processes. Each of these genes has vertebrate homologues and we believe that understanding how these genes act in C. elegans will be directly applicable to neural circuit control in vertebrates. We use genetic and biochemical approaches to identify novel genes that act together or downstream of these genes to determine and specify neural circuits in C. elegans.