{"doi":"10.1242/dev.204965","title":"Mouse scalp development requires Rac1 and SRF for the maintenance of mechanoresponsive mesenchyme","abstract":"Rac1 is a small GTPase that regulates cell proliferation, migration and differentiation processes crucial for development. Mutations in specific guanine nucleotide exchange factors and GTPases that regulate Rac1 are associated with Adams-Oliver syndrome (AOS), a syndrome characterized by congenital scalp defects and limb truncations. Rac1 deletion in mouse embryonic limb ectoderm causes limb truncation. However, the etiology of Rac1-associated cranial defects is unknown. To investigate the cranial defects, we used Pdgfra-Cre to delete Rac1 in cranial mesenchyme. Rac1-KO mice died perinatally and lacked the apical calvarium and overlying dermis, resembling defects seen in severe AOS. In control embryos, α-smooth muscle actin (αSMA) expression was spatially restricted to the apical mesenchyme, suggesting mechanical interactions between the growing brain and the overlying mesenchyme. In Rac1-KO embryos, proliferation of apical mesenchyme, and expression of αSMA and its regulator, serum response factor (SRF), were reduced. Remarkably, Srf-KO with Pdgfra-Cre recapitulated the phenotype observed in Rac1-KO mice. Together, these data suggest a model where Rac1 and SRF maintain apical fibroblasts in a mechanoresponsive and proliferative state to complete cranial development.","journal":"Development","year":2025,"id":578848,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9514,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":853897,"name":"Alex Rackley","orcid":null,"position":1,"is_corresponding":false},{"id":757004,"name":"Hae Ryong Kwon","orcid":"0000-0002-0428-3971","position":2,"is_corresponding":false},{"id":309310,"name":"Jang Kim","orcid":"0000-0003-3510-5956","position":3,"is_corresponding":false},{"id":309312,"name":"William L. Berry","orcid":"0000-0002-1661-5443","position":4,"is_corresponding":false},{"id":309314,"name":"Lorin E. Olson","orcid":"0000-0003-2168-7836","position":5,"is_corresponding":false},{"id":853099,"name":"Bharath H. Rathnakar","orcid":"0000-0001-7605-0870","position":0,"is_corresponding":true}],"reference_count":91,"raw_metadata":null,"created_at":"2026-07-19T02:58:24.957414Z","pmid":"41126757","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":[]}