{"doi":"10.1101/2022.08.04.502867","title":"Distinct hyperactive RAS/MAPK alleles converge on common GABAergic interneuron core programs","abstract":"Abstract RAS/MAPK gene dysfunction underlies various cancers and neurocognitive disorders. While the role 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+. The increase in somatostatin+ interneurons could also be induced by elevated neural activity and we show the core RAS/MAPK signaling pathway is one mechanism by which this occurs. 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/disorders.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":298337,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9536,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":987312,"name":"April M Stafford","orcid":"0000-0001-8312-4380","position":1,"is_corresponding":false},{"id":987313,"name":"Tariq Zaman","orcid":"0000-0003-1025-8542","position":2,"is_corresponding":false},{"id":275004,"name":"Roxan Ara","orcid":"0000-0002-6334-9301","position":3,"is_corresponding":false},{"id":795225,"name":"Michael R. Williams","orcid":"0000-0003-3310-7181","position":4,"is_corresponding":false},{"id":395703,"name":"Jason M. Newbern","orcid":"0000-0003-2865-0112","position":5,"is_corresponding":false},{"id":331768,"name":"Daniel Vogt","orcid":"0000-0003-1876-5936","position":6,"is_corresponding":false},{"id":395693,"name":"Sara Knowles","orcid":"0000-0003-3906-8195","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-19T00:31:36.269611Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}