Neurotransmitter receptors regulate ecdysteroid biosynthesis and developmental transition in Drosophila. Yuko Shimada¹, Yosuke Umei¹, Jevgenija Maramzina¹, Ryusuke Niwa^1,2. 1) Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan; 2) PRESTO, JST, Japan.

   The Insect principal steroid hormones, ecdysteroids, play crucial roles in many aspects of development. During larval stages, ecdysone is synthesized from dietary cholesterol in the specialized endocrine organ called the prothoracic gland (PG). Ecdysteroid biosynthesis is influenced by several external conditions, such as nutrition, temperature, and photoperiod, which lead to flexible alterations of developmental timing accompanied with molting and metamorphosis. However, it remains unclear how external information is transmitted to the PG to adaptively control the ecdysteroidogenic enzymes. To uncover genes involved in controlling the ecdysteroid biosynthesis in the PG, we conducted a transgenic RNAi screen using the PG-specific GAL4 drivers and UAS-RNAi strains. We found that developmental arrests were caused by RNAi for genes encoding some neurotransmitter receptors. These phenotypes were rescued when the RNAi animals were fed 20-hydroxyecdysone. Moreover, the ecdysteroid titer and the expression levels of ecdysteroidogenic enzyme genes significantly decreased in the RNAi animals. These results suggest that these neurotransmitter receptors are essential for ecdysteroid biosynthesis. Interestingly, a subset of neurons, which was different from the previously-identified PTTH neurons, directly innervated to the PG. The dendrites of these neurons extended toward the subesophagal ganglion, known as the insect feeding center, implying that these neurons receive signals related to food. Consistently, the projection of the neurons to the PG was affected by nutrient condition. Moreover, genetic manipulations inhibiting the projection into the PG resulted in a delayed pupariation. Considering that neurotransmitters modulate neuronal activities in response to external stimuli, we currently hypothesize that the neurotransmitters and their receptors play important roles in reflecting environmental conditions on ecdysteroid biosynthesis in the PG.