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0Researchers have developed a sophisticated in vivo AAV-Perturb-seq platform to investigate the biological functions of major depressive disorder (MDD) risk genes within the mouse brain. By performing high-throughput loss-of-function screening on dozens of candidates identified through human genetic studies, the team successfully mapped how these genes influence neuronal gene expression and synaptic signaling. Their analysis pinpointed a specific MDD risk cluster, featuring the gene Dennd1a, which produces a transcriptomic signature remarkably similar to those found in human patients. Experimental evidence showed that silencing Dennd1a in neurons impairs the oxytocin receptor pathway and triggers depressive-like behaviors in mice. Ultimately, the study demonstrates that pharmacological restoration of this signaling pathway can reverse these effects, highlighting a potential avenue for personalized psychiatric treatments.
References:
Zhang L, Kong X, Ma Q, et al. Linking GWAS risk genes to transcriptional features of major depressive disorder via in vivo Perturb-seq[J]. Nature Genetics, 2026: 1-13.
