The Corazonin-PTTH Neuronal Axis Controls Systemic Body Growth by Regulating Basal Ecdysteroid Biosynthesis in  <i>Drosophila melanogaster</i>

Abstract

Growth and maturation are coordinated by steroid hormone biosynthesis in various animal phyla. The insect steroid hormone, ecdysteroid, coordinates growth and maturation, represented by molting and metamorphosis. In Drosophila melanogaster, prothoracicotropic hormone (PTTH) neurons stimulate in generating peak levels of ecdysteroid to trigger maturation. In addition, recent studies have shed light on the role of PTTH signaling in basal ecdysteroid biosynthesis, which negatively affects systemic growth prior to maturation. However, it remains unclear how PTTH signaling is regulated for basal ecdysteroid biosynthesis. Here, we report that Corazonin (Crz)-producing neurons regulate basal ecdysteroid biosynthesis by affecting PTTH neurons. Inhibition of Crz neuronal activity increased pupal size, whereas it had little effect on pupariation timing. This phenotype resulted from enhanced growth and a delay in basal ecdysteroid elevation during the mid-third instar larval (L3) stage. Silencing of Crz in Crz neurons resulted in increased levels of the microRNA bantam, which represses basal ecdysteroid biosynthesis. Interestingly, Crz receptor (CrzR) expression in PTTH neurons was higher during the mid- than during the late-L3 stage. Silencing of CrzR in PTTH neurons increased pupal size, phenocopying the inhibition of Crz neuronal activity. When Crz neurons were optogenetically activated, a strong calcium response was observed in PTTH neurons in the mid-, but not the late-L3 stage. These data suggest that the Crz-PTTH neuronal axis modulates basal, but not peak ecdysteroid biosynthesis. Most significantly, this study uncovered a regulatory neuronal system affecting ecdysteroid biosynthesis in a developmental stage-specific manner.