Distinct hyperactive RAS/MAPK alleles converge on common GABAergic interneuron core programs

• DOI: 10.1242/dev.201371
• Publication Date: 2023-05-11T13:24:38Z
• Authors: Sara J. Knowles; April M. Stafford; Tariq Zaman; Kartik Angara; Michael R. Williams; Jason M. Newbern; Daniel Vogt
• Keywords: Interneuron

RAS/MAPK gene dysfunction underlies various cancers and neurocognitive disorders. While the role of genes have been well studied in cancer, less is known about their function during neurodevelopment. There are many that work concert to regulate signaling, suggesting if common brain phenotypes could be discovered they a broad impact on other disorders caused by distinct genes. We assessed cellular molecular consequences hyperactivating pathway using two cell type previously implicated RAS/MAPK-mediated cognitive changes, cortical GABAergic interneurons. uncovered some core programs commonly altered each mutants. Notably, hyperactive mutants bias developing interneurons towards those somatostatin+. The increase somatostatin+ also induced elevated neural activity we show signaling one mechanism which this occurs. Overall, these findings present new insights into how different mutations can converge interneurons, may important for genes/disorders.