Affiliation: Immunology program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, NY, NY, USA.
Keywords: e. endocrine function; h. hemocytes
Disturbances during development are sensed by monitoring hormones and signals released from the impaired tissues. All developing tissues and organs have the ability to release and receive information about the growth status of themselves or the different parts of the body. This communication mechanism involves hormones, peptides, and metabolites. Recent evidence suggests that macrophages act as a multi-organ rheostat that constantly senses and monitors homeostasis. Moreover, macrophages have the ability to relay signals, as growth factors, to mitigate perturbations and restore homeostasis during development. Recent studies from my host lab demonstrated that flies lacking macrophages disrupt the developmental transition between juvenile (larva) to puberty (pupa) stages. Developmental timing is regulated by sterols hormones synthesis in endocrine glands. However, how macrophages sense perturbations (such as nutrition) and communicate with the neuroendocrine system to control developmental timing remains unsolved.
In this presentation, we will discuss how macrophages communicate with the neuroendocrine system. First, we proved that the lack of macrophages during development regulates the sterol hormone synthesis (ecdysone) in the prothoracic gland by reducing the Halloween genes transcription. To further understand how macrophages regulate ecdysone synthesis, we carried out a knockdown genetic screen of growth factors secreted by macrophages during development. We obtained Pvf2 as a factor required in macrophages to control developmental timing. Reduction of pvf2 expression in macrophages induces developmental delay by reducing Halloween genes transcription and ecdysone synthesis. Moreover, the lack of Pvf2 receptor, pvr, in the prothoracic gland induces developmental delay by ecdysone production inhibition. In addition, the lack of pvf2 in macrophages reduces their total number in larva stages, suggesting a mechanism where Pvr monitors the total number of macrophages in the body through Pvf2 before ecdysone pulse turn up for developmental transition in L3-instar larvae. The pvf2-depleted macrophages phenotypes are recapitulated in the pvf2 null mutant. The developmental delay and ecdysone synthesis inhibition in pvf2 null mutant were rescued by overexpression of pvf2 in macrophages or pvr in the prothoracic gland. Therefore, our data suggest a communicative process between macrophages and the neuroendocrine system involving Pvf2/Pvr to fine-tune ecdysone synthesis in the larva to pupa transition.