The nuclear receptor DHR3/Hr46 is required in the blood brain barrier of mature males for courtship

Abstract

The blood brain barrier (BBB) forms a stringent barrier that protects the brain from components in the circulation that could interfere with neuronal function. At the same time, the BBB enables selective transport of critical nutrients and other chemicals to the brain. Many of these processes are still poorly understood. Beyond these functions, another recently recognized function is even less characterized, specifically the role of the BBB in modulating behavior by affecting neuronal function in a sex dependent manner. Notably, signaling in the adult Drosophila BBB is required for normal male courtship behavior. Courtship regulation also relies on male-specific molecules in the BBB. Our previous studies have demonstrated that adult feminization of these cells in males significantly lowered courtship. Here, we conducted microarray analysis of BBB cells isolated from males and females. Findings revealed that these cells contain male- and female-enriched transcripts, respectively. Among these transcripts, nuclear receptor DHR3/Hr46 was identified as a male-enriched BBB transcript. DHR3/Hr46 is best known for its essential roles in the ecdysone response during development and metamorphosis. In this study, we demonstrate that DR3/Hr46 is specifically required in the BBB cells of mature males for courtship behavior. The protein is localized in the nuclei of sub-perineurial glial cells (SPG), indicating that it might act as a transcriptional regulator. These data provide a catalogue of sexually dimorphic BBB transcripts and demonstrate a physiological adult role for the nuclear receptor DH3/Hr46 in the regulation of male courtship, a novel function that is independent of its developmental role. Author summaryThe blood brain barrier very tightly regulates which molecules can enter the brain. This is an important protection for the brain, however, it also complicates communication between molecules in the circulating fluid and the brain. In fly courtship, for example, circulating male-specific products are crucially required for normal courtship. But the neuronal circuits that ultimately control the behavior are inside the brain, separated from these molecules by the blood brain barrier. The mechanisms of this communication are not known. Here we show that the blood brain barrier itself contains sex-specific RNAs and we show that one of them, a nuclear receptor called DHR3, is required in adult males for normal courtship. These findings promise new insight into the communication between blood brain barrier and the brain.