Studies on the Neuropeptide Allatostatin-C Pathways that Regulate Oogenesis in Drosophila melanogaster

Abstract

Oogenesis is essential for reproduction. In the fruit fly Drosophila melanogaster, vitellogenesis (i.e., yolk protein biosynthesis and accumulation) is the major control point of oogenesis. Vitellogenesis initiates upon eclosion and continues during the development of sexual maturation. It is also stimulated by a mating signal or sex peptide (SP), the key seminal substance that triggers robust oogenesis and oviposition activity. Unlike oviposition, which is stimulated strongly by light and dark transition, oogenesis has circadian rhythmicity that runs in constant darkness (DD) condition. However, it is unknown how the central nervous system (CNS) generates the rhythm and regulates oogenesis according to developmental and reproductive contexts. In the first part of my thesis study, I investigated a subset of the group of neurons in the brain named as “posterior dorsal neuron 1” (AstC-DN1p) that produce the neuropeptide allatostatin C (AstC). I discovered that the neural activity of AstC-DN1p and AstC neuropeptide are essential for generating the oogenesis rhythm under DD condition. This pathway suppresses the biosynthesis of juvenile hormone (JH), an endocrine stimulator of vitellogenesis, indirectly by inhibiting insulin signaling through two AstC receptors (AstC-R1 and -R2) expressed in insulin-producing cells (IPCs). In the second part, I identified a pair of thoracic ganglion neurons expressing AstC (AstC-mTh), which inhibits JH biosynthesis of JH through both AstC receptors expressed in corpora allatum (CA), an endocrine organ that synthesizes and secretes JH. I showed that AstC-mTh neurons regulate post-mating vitellogenesis initiation. In the mated females, SP inhibits AstC-mTh activity and then relieves the inhibitory input of AstC on the CA, allowing JH biosynthesis and progression of vitellogenic oocyte development. AstC is orthologous to the vertebrate neuropeptide somatostatin (SST). SST also inhibits the secretion of gonadotrophin indirectly through gonadotropin releasing hormone (GnRH) neurons in the hypothalamus. The structural and functional conservations between AstC and SST strongly suggests an ancestral origin of AstC/SST neuropeptide pathways that function as negative regulators of gonadotropins. In summary, my thesis uncovered that the highly conserved neuropeptide pathways modulate insect gonadotropin JH levels and oogenesis according to the circadian rhythm and mating state.