The long term objective of this project is to uncover the molecular mechanisms by which neuronal connections are formed. Improper formation of neuronal connectivity is thought to be the cause of numerous neural disorders. Understanding the molecular mechanisms underlying such diseases would permit the design of a rational treatment to prevent these disorders. Furthermore, understanding how connections are formed may allow the development of treatments to induce regeneration in patients suffering from neurodegenerative and neuromuscular disorders. Experiments in the Drosophila neuromuscular system suggest that molecules expressed by the muscle target are essential for motoneuron target recognition and synaptic development. The goal of this project is to find these molecules. Genes will be sought based on indicator transgenes, known as enhancer traps, that are expressed in muscles near the time of innervation. Molecular and functional analysis will be performed to ascertain what function these genes play in neuron-muscle recognition and synapse development. A mosaic method will be developed to analyze gene function directly in the muscle targets. Using these methods, target recognition genes will be obtained regardless of their role outside the muscle, overcoming a serious limitation of classical genetic screens.
