The unique ability of chemical synapses to transmit information relies on the structural organization of presynaptic terminals. Empowered by forward genetics, research using Caenorhabditis elegans has continued to make pivotal contributions to discover conserved regulators and pathways for presynaptic development. Recent advances in microscopy have begun to pave the path for linking molecular dynamics with subsynaptic structures. Studies using diverse reporters for synapses further broaden the landscape of regulatory mechanisms underlying presynaptic differentiation. The identification of novel regulators at transcriptional and post-transcriptional levels raises new questions for understanding synapse formation at the genomic scale.
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