Genetic analysis of morphological and functional synapse growth at the Drosophila NMJ.

摘要

Nerve cells contact each other at synapses and communicate via synaptic transmission. Once they form synapses are not static, but continue to grow during development, plasticity and disease. Combining genetic and cell biological tools at the Drosophila neuromuscular junction (NMJ), I isolated a number of mutations and signaling pathways regulating morphological and functional synapse growth. In my introduction I define the terms morphological and functional synapse growth as well as review our current knowledge of these topics. In the first chapter, I characterize the nerve-wracked mutation, which disrupts synaptic bouton formation. Second, I describe bad hair day, a novel gene encoding a chromatin-remodeling factor that is involved in suppression of satellite bouton formation. Next, I demonstrate that the Drosophila NF-kappa B pathway regulates GluR abundance via a novel, cytoplasmic mechanism. Finally, I suggest that cytoplasmic NF-kappaB/Dorsal acts upstream of Pelle kinase, which regulates insertion of GluR into the synaptic membrane. These findings reveal some of the molecular mechanisms in place during synapse growth, and may have implications for understanding synaptic plasticity and disease.