Refinement of neural circuits during development requires formation and elimination of synaptic connections, a process governed by activity-dependent mechanisms and developmental genetic programs. Bone Morphogenetic Protein (BMP) retrograde signaling through the type II receptor Wishful thinking (Wit) is essential for synaptic growth and functional development of the Drosophila larval neuromuscular junction. However, little is known about the genes that are regulated by the pathway to effect synaptic growth and proper synaptic transmission. We have identified a transcriptional target of wit (twit), whose expression in motoneurons depends on Wit activity. Null twit mutants are viable and fertile, but recapitulate some of the electrophysiological phenotypes of wit mutants, such as decreased frequency and amplitude of miniature excitatory junction potentials. Other wit phenotypes, such as decreased synaptic terminal size and evoked excitatory junction potentials, are not found in twit mutants, suggesting that homeostatic compensation of presynaptic release is intact in twit mutants and that Wit regulates additional genes to accomplish proper synaptic maturation. Twit is a glycosylphosphatidylinositol-anchored protein of the Lymphocyte antigen 6 family (Ly-6), and neuronal expression of a twit transgene rescues twit's mutant phenotypes. Importantly, twit expression partially rescues diminished frequency of miniature excitatory synaptic potentials in wit mutants. This further supports the conclusions that Twit is signaling in larval motoneurons and an essential effector of the retrograde BMP signal. Taken together, our results suggest that retrograde BMP signaling regulates spontaneous neurotransmitter release by activating the transcription of the Ly-6 gene twit.
- Synaptic development
- Wishful thinking