9807933 GRANATO The enormous amount of information processed in the nervous system is dependent on a complex network of trillions of neuronal connections. These neural connections are formed during embryogenesis, when neurons extend axonal projections to their targets. Axonal growth occurs in a highly precise and stereotypic fashion. The objective of this project is to determine the cellular and molecular mechanisms by which motor axons extend out from the spinal cord to reach their distant muscle targets. The laboratory of Dr. Granato uses the zebrafish (Danio rerio) to investigate molecular and cellular aspects of axonal growth and guidance. Dr. Granato has previously isolated mutations in over 30 genes with diverse functions in neurons that are part of the neuronal circuits mediating locomotion. This project focuses on one of these genes, called diwanka. In diwanka mutant embryos, the axons from motor neurons in the trunk region of the fish fail to extend to their muscle targets, whereas other axonal projections are unaffected by mutations in the diwanka gene. This suggests that the diwanka gene plays a crucial and specific role in guiding motor axons. In the current experiments, Dr. Granato will investigate where in the long motor axonal pathway from the spinal cord to specific muscles targets the diwanka gene is required. He will also determine if the diwanka gene functions as a muscle derived cue to attract motor axons. Finally, he will use molecular methods to uncover the precise chromosomal region of the diwanka gene. Results from the project will enhance our understanding how axons migrate towards their distant targets and will also provide the tools to uncover the molecular identity of the diwanka gene. These experiments are likely to reveal unknown molecules and mechanisms involved in the precise guidance of axons to their targets.
