The histone acetyltransferase Elp3 plays in active role in the control of synaptic bouton expansion and sleep in Drosophila

P>The histone acetyltransferase Elp3 (Elongator Protein 3) is the catalytic subunit of the highly conserved Elongator complex. Elp3 is essential for the complex functions of Elongator in both the nucleus and cytoplasm of neurons, including the epigenetic control of neuronal motility genes and the acetylation of alpha-tubulin that affects axonal branching and cortical neuron migration. Accordingly, misregulation of Elp3 has been implicated in human disorders that specifically affect neuronal function, including familial dysautonomia, a disease characterized by degeneration of the sensory and autonomic nervous system, and the motor neuron degenerative disorder amyotrophic lateral sclerosis. These studies underscore the importance of Elp3 in neurodevelopment and disease, and the need to further characterize the multiple nuclear and cytoplasmic based roles of ELP3 required for neurogenesis in animal models, in vivo. In this report, we investigate the behavioral and morphological consequences that result from targeted reduction of ELP3 specifically in the developing Drosophila nervous system. We demonstrate that loss of Elp3 during neurodevelopment leads to a hyperactive phenotype and sleep loss in the adult flies, a significant expansion in synaptic bouton number and axonal length and branching in the larval neuromuscular junction as well as the misregulation of certain genes known to be involved in these processes. Our results uncover a novel role for Elp3 in the regulation of synaptic bouton expansion during neurogenesis that may be linked with a requirement for sleep.