Regulatory Mechanisms of Metamorphic Neuronal Remodeling Revealed Through a Genome-Wide Modifier Screen in Drosophila melanogaster .

During development, neuronal remodeling shapes neuronal connections to establish fully mature and functional nervous systems. Our previous studies have shown that the RNA-binding factor () is an important regulator of neuronal remodeling during metamorphosis in , and loss of leads to smaller soma size and fewer neurites in a stage-dependent manner. To shed light on the mechanisms by which regulates neuronal remodeling, we conducted a genetic modifier screen for suppressors of -dependent wing expansion defects and cellular morphological defects in a set of peptidergic neurons, the bursicon neurons, that promote posteclosion wing expansion. Out of 702 screened deficiencies that covered 86% of euchromatic genes, we isolated 24 deficiencies as candidate suppressors, and 12 of them at least partially suppressed morphological defects in mutant bursicon neurons. With RNA interference and mutant alleles of individual genes, we identified () and () as suppressor genes, and both of them restored the adult cellular morphology of -depleted bursicon neurons. encodes an inhibitory Smad protein that inhibits bone morphogenetic protein (BMP) signaling, raising the possibility that interacted with BMP signaling through antagonism of By manipulating expression of the BMP receptor , we found that activated BMP signaling was sufficient to rescue loss-of- phenotypes. These findings reveal mechanisms of regulation during neuronal development, and they highlight a novel genetic interaction with the BMP signaling pathway that controls morphogenesis in mature, terminally differentiated neurons during metamorphosis.