Abrupt-mediated control of ninjurins regulates Drosophila sessile haemocyte compartments

Macrophage-like cells called haemocytes are key effectors of Drosophila cellular innate immune function. Larval haemocytes exist either in circulation or localize to segmentally repeated sessile haemocyte compartments (SHCs). While numerous functions have been proposed for SHCs, the mechanisms directing haemocytes to them are unclear. Here, we have exploited the developmentally regulated dispersal of SHCs that occurs at pupariation to identify the Abrupt (Ab) transcription factor (TF) and ninjurin cell-adhesion molecules as regulators of haemocyte recruitment to SHCs. We show that larval haemocytes express ninjurins, which are required for targeting haemocytes to SHCs. However, at pupariation, ecdysteroid signalling stimulates Ab expression, which collaborates with TFs, including Blimp-1 and Hr3, to repress ninjurins and disperse haemocytes. We observe that experimental manipulations that antagonize ninjurin function in larval haemocytes cause premature SHC dispersal, while stabilization of ninjurins in haemocytes blocks developmentally regulated SHC remodelling and increases sensitivity to immune challenges. Cumulatively, our data indicate that control of ninjurin activity provides a common target through which diverse developmental, environmental and immune stimuli can be integrated to control haemocyte dispersal and immune function.