Affiliation: University of Virginia, Charlottesville, VA
Keywords: l. Insulin signaling/ insulin-like peptides; j. fat body
The Drosophila larval fat body regulates growth of the whole animal in response to dietary nutrients, hormonal cues, and physiological stressors such as infection. The allocation of resources to growth and nutrient storage and the secretion of endocrine growth factors such as Dilp6 underlie fat body-dependent growth regulation. Indeed, our previous work showed that innate immune signaling in larval fat body targets Dilp6 to inhibit peripheral growth. To identify novel regulators of growth, we performed a directed genetic screen targeting transcription factors expressed in larval fat body. We screened for transcription factors that regulate peripheral growth basally and in response to active innate immune signaling in fat body. In a related screen, we queried a set of transcription factors shown to physically interact with the Dilp6 promoter using data from the ENCODE consortium. These screens identify novel regulators of whole-animal growth such as the transcription factor pleiohomeotic like (phol), which modifies growth inhibition resulting from Toll signaling in larval fat body. Additionally, by screening predicted transcriptional regulators of Dilp6, we identified that increased expression of hairy (h) in fat body from the mid-third instar through the white prepupal stage reduces Dilp6 transcript levels. In contrast, fat body-specific knockdown of daughterless (da) suppresses Dilp6 expression in mid-third instar larvae but not in white prepupae. These two screens have identified discrete regulators that participate in Toll-dependent growth inhibition and Dilp6 regulation. Indeed, previous data from our lab indicate that reduced Dilp6 secretion in animals with active fat body Toll signaling does not account for the full degree of growth inhibition in these animals. Furthermore, our data point to additional, unappreciated signaling pathways that contribute to developmentally-appropriate regulation of Dilp6.