HBL-1 Patterns Synaptic Remodeling in C-elegans

During development, circuits are refined by the dynamic addition and removal of synapses; however, little is known about the molecular mechanisms that dictate where and when synaptic refinement occurs. Here we describe transcriptional mechanisms that pattern remodeling of C. elegans neuromuscular junctions (NMJs). The embryonic GABAergic DD motor neurons remodel their synapses, whereas the later born VD neurons do not. This specificity is mediated by differential expression of a transcription factor (HBL-1), which is expressed in DD neurons but is repressed in VDs by UNC-55/COUP-TF. DD remodeling is delayed in hbl-1 mutants whereas precocious remodeling is observed in mutants lacking the microRNA mir-84, which inhibits hbl-1 expression. Mutations increasing and decreasing circuit activity cause corresponding changes in hbl-1 expression, and corresponding shifts in the timing of DD plasticity. Thus, convergent regulation of hbl-1 expression defines a genetic mechanism that patterns activity-dependent synaptic remodeling across cell types and across developmental time.