bantam miRNA promotes systemic growth by connecting insulin signaling and ecdysone production

During the development of multicellular organisms, body growth is controlled at the scale of the organism by the activity of long-range signaling molecules, mostly hormones. These systemic factors coordinate growth between developing tissues and act as relays to adjust body growth in response to environmental changes [1]. In target organs, long-range signals act in concert with tissue-autonomous ones to regulate the final size of a given tissue. In Drosophila, the steroid hormone ecdysone plays a dual role: peaks of secretion promote developmental transitions and maturation, while basal production negatively controls the speed of growth. The antagonistic action of ecdysone and the conserved insulin/insulin growth factor (IGF) signaling pathway regulate systemic growth and modulate final body size [2, 3]. Here we unravel an unexpected role of bantam microRNA in controlling body size in Drosophila. Our data unveil that, in addition to its well-characterized function in autonomously inducing tissue growth [4-9], bantam activity in ecdysone-producing cells promotes systemic growth by repressing ecdysone release. We also provide evidence that the regulation of ecdysone production by insulin signaling relies on the repression of bantam activity. These results identify a molecular mechanism that underlies the crosstalk between these two hormones and add a new layer of complexity to the well-characterized role of bantam in growth control.