ROLE OF EPH RECEPTORS AND THEIR LIGANDS IN CELL PATTERNING

Receptor tyrosine kinases were originally identified as cellular homologs of viral oncogenes that elicit cellular transformation. Receptor tyrosine kinases play essential roles in cell signaling and lead to diverse cellular processes, including cell proliferation, differentiation, and survival. A large new subfamily of receptor tyrosine kinases, the Eph family, may be responsible for a unique array of cellular properties, including cell migration, cell adhesion, and axon guidance affording cell information as to where they are and who their neighbors are. In this manner, alterations in the Eph receptor ligand system may contribute to disarray in cell growth and cell migration characteristic of the tumor phenotype. We are studying a specialized set of olfactory neurons, the vomeronasal sensory neurons that undergo cell migration, compartment formation and axon outgrowth to form a complex topographic map. Interestingly, these cells reside within distance compartments that are defined by the nature of the Eph ligands that they express. The highly specialized nature of this set of neurons has permitted us to manipulate this system to genetically examine the role of the Eph receptors and their ligands in these cells without major effect upon the development or reproductive status of the organism. Experiments are designed to discern the cellular and molecular mechanisms of Eph receptor signaling, and how these signals result in cell patterning. These genetic approaches in this specialized neuronal system may be more generally applicable to cellular processes outside of the nervous system.