Abstract
Synaptic development and functionality have been considered as fundamental mechanisms underlying a range of neuropsychiatric disorders, including schizophrenia. Emerging evidence from biological and clinical studies implicates mutations in the Disrupted-in-Schizophrenia-1 (DISC1) gene in the pathogenesis of schizophrenia. In this study, genetic interactions among a select set of risk factor genes are examined using the unique model system: neuromuscular junctions (NMJs) in Drosophila. We found that dnlg1, the Drosophila homolog of the human Neuroligin-1, which encodes the NLGN1 protein, genetically interacts with DISC1 in synaptic development. We show that DISC1 overexpression in the dnlg1[null] heterozygous background causes synaptic alterations at the NMJs that are distinct from those in the wild-type background. Loss of dnlg1 enhanced the DISC1 overexpression phenotype in synaptic formation, strongly suppressing the formation of synaptic boutons. These results thus suggest an intriguing converging mechanism regulated by DISC1 and Neuroligin in the developing glutamatergic synapses.
