During development, some cells must migrate to distant sites before dividing and differentiating. In the developing nervous system, precise patterns of synaptic connections are formed as pioneering axons migrate to find their correct target regions. Our goal is to understand how axon and cell migrations are guided.
Our research employs the powerful genetic and molecular techniques available to study development and function in the nematode C. elegans. The unc-6 gene is required for guiding dorsal and ventral migrations on the basal surface of the epidermis. This gene encodes a novel laminin-related extracellular matrix protein. A family of vertebrate axon outgrowth-promoting proteins, the netrins, are homologous to UNC-6. The analysis of UNC-6 in the nematode and of the netrins in the developing spinal cord indicate these molecules guide circumferential axon migrations. As a simple hypothesis, UNC-6/netrin is a secreted matrix guidance cue which is tracked by receptors expressed on the surface of migrating cells. This model provides the basis to study structural arrangements and biological properties of the various components which comprise this guidance system. This laboratory is studying the spatial and temporal expression of UNC-6, is studying structure /function relationships using transgenic strains expressing netrin or UNC-6 mutant alleles, and is studying biochemical relationships between UNC-6, netrin, and other extracellular matrix proteins.