Adamts-family protease mig-17 regulates synaptic allometry by modifying the extracellular matrix and modulating glia morphology during growth

Synapses are largely established during embryogenesis and maintained during growth. The mechanisms that regulate synaptic allometry—the upkeep of synaptic positions during growth—are largely unknown. We performed forward genetic screens in C. elegans for synaptic allometry mutants and identified mig-17, a secreted metalloprotease from the conserved ADAMTS family. Through proteomic mass spectrometry analyses, cell biological and genetic studies we determined that MIG-17 is expressed by muscle tissues to modulate glia location and morphology. Glia are proximal to synapses, and also the glial location and morphology determine synaptic position during growth. Mig-17 regulates synapse allometry by influencing epidermal-glia crosstalk with the regulating basement membrane proteins, including bovine collagen type IV, SPARC and fibulin. Our findings underscore the significance of glia location within the upkeep of synaptic allometry, and uncover a muscle-epidermal-glia signaling axis, mediated with the extracellular matrix, within the regulating glia morphology and synaptic positions during growth.