| First Author | Knowles SJ | Year | 2023 |
| Journal | Development | Volume | 150 |
| Issue | 10 | PubMed ID | 37254876 |
| Mgi Jnum | J:336092 | Mgi Id | MGI:7486437 |
| Doi | 10.1242/dev.201371 | Citation | Knowles SJ, et al. (2023) Distinct hyperactive RAS/MAPK alleles converge on common GABAergic interneuron core programs. Development 150(10):dev201371 |
| abstractText | RAS/MAPK gene dysfunction underlies various cancers and neurocognitive disorders. Although the roles of RAS/MAPK genes have been well studied in cancer, less is known about their function during neurodevelopment. There are many genes that work in concert to regulate RAS/MAPK signaling, suggesting that if common brain phenotypes could be discovered they could have a broad impact on the many other disorders caused by distinct RAS/MAPK genes. We assessed the cellular and molecular consequences of hyperactivating the RAS/MAPK pathway using two distinct genes in a cell type previously implicated in RAS/MAPK-mediated cognitive changes, cortical GABAergic interneurons. We uncovered some GABAergic core programs that are commonly altered in each of the mutants. Notably, hyperactive RAS/MAPK mutants bias developing cortical interneurons towards those that are somatostatin positive. The increase in somatostatin-positive interneurons could also be prevented by pharmacological inhibition of the core RAS/MAPK signaling pathway. Overall, these findings present new insights into how different RAS/MAPK mutations can converge on GABAergic interneurons, which may be important for other RAS/MAPK genes and related disorders. |
