Neurexin and neuroligin loss drives system-wide transcriptional reprogramming in Caenorhabditis elegans

Here, we show that loss of neurexin (nrx-1) or neuroligin (nlg-1) in Caenorhabditis elegans drives system-wide transcriptional reprogramming. Mutants exhibited impaired growth, altered locomotion, increased repetitive behavior, increased social aggregation, and reduced ventral nerve cord neuronal integrity.

Transcriptome profiling revealed coordinated downregulation of genes involved in structural development, synaptic signaling, and protein homeostasis, alongside upregulation of stress-response, immune, and metabolic pathways. These changes define a shift from developmental and synaptic programs toward stress-adaptive states, accompanied by signatures of mitochondrial remodeling. Notably, nrx-1 mutants displayed more pronounced effects.