Neuronal E93 is required for adaptation to adult metabolism and behavior

Abstract

Metamorphosis is a transition from growth to reproduction, through which an animal adopts adult behavior and metabolism. Yet the neural mechanisms underlying the switch is unclear. Here we report that neuronal E93, a transcription factor essential for metamorphosis, regulates the adult metabolism, physiology, and behavior in Drosophila melanogaster. Identified from a screen designed to find new neuronal regulators of metabolism, E93 is required to control appetite, metabolism, exercise endurance, and circadian rhythms. An additional screen of Gal4 lines targeting subsets of neurons or endocrine cells identified neurons producing GABA and myoinhibitory peptide (MIP) as the main sites of E93 action. Knockdown of the ecdysone receptor specifically in MIP neurons partially phenocopies the MIP neuron-specific knockdown of E93, suggesting the steroid signal coordinates adult metabolism via E93 and a neuropeptidergic signal. The diverse phenotypes caused by pan-neuronal knockdown of E93, including obesity, exercise intolerance and circadian disruption, can all be phenocopied by knockdown of E93 specifically in either GABA or MIP neurons, suggesting these neurons are key sites or E93 action. Finally, E93 in GABA and MIP neurons also serves as the key switch for the adaptation to adult behavior, as animals with reduced expression of E93 in the two subsets of neurons exhibit reduced reproductive activity. Our study reveals that E93 is a new monogenic factor essential for metabolic, physiological, and behavioral adaptation from larval behavior to adult behavior.