The goal of the research is to understand cellular interactions that occur during cell migration and axon outgrowth in a vertebrate. Cell migration and axon outgrowth play a major role in vertebrate development, yet we know very little about the mechanisms involved. These studies are designed to take advantage of a simple, accessible system in a simple vertebrate in order to learn about fundamental mechanisms of development. The studies are focused on the developing posterior lateral line system of embryonic zebrafish. Lateral line receptors arise by a remarkable and stereotyped migration of cells within the skin. As these cells migrate, growth cones of sensory neurons comigrate with them. These sensory neurons will later be in synaptic contact with the migrating cells. The studies proposed here will test hypotheses concerning guidance of the growth cones and of the migrating cells. In particular, two hypotheses will be tested: (a) that the growth cones are led by their migrating target cells in their peripheral migration, and (b) that the migrating cells are in turn guided by cues associated with the underlying myotomes. We propose (1) to identify the substrate that the growth cones migrate on by observing their behavior as they migrate along their normal pathway in the living animal, and to study them by electron microscopy; (2) to determine whether the migrating cells lead or follow the growth cones by ablation studies, and by observing the growth cones as the primordium migrates along abnormal pathways, and (3) to determine whether the myotomes underlying the skin along the migration pathway play a role in directing the cell migration.
