{"doi":"10.1101/2025.11.03.686369","title":"Genetic interaction of <i>Specc1l</i> and <i>Thm1</i> reveals cytoskeletal - ciliary crosstalk","abstract":"Cilium formation and actin cytoskeleton dynamics are interconnected, with evidence showing that elevated filamentous actin (F-actin) negatively regulates primary cilia length. Loss of the cytoskeletal protein SPECC1L, which itself does not localize to cilia, leads to increased F-actin and shortened cilia. Depolymerizing F-actin in Specc1l mutant cells restored cilia lengths, substantiating this inverse relationship. In cells harboring a Specc1l allele lacking only the coiled-coil domain 2, intracellular regions with both elevated and reduced F-actin were observed together with cilia shortening. Notably, F-actin was decreased at the ciliary base, suggesting that a different F-actin subpopulation contributes to the inverse relationship. We also identified a genetic interaction between Specc1l and Thm1 , which encodes an intraflagellar transport-A (IFT-A) protein. Double or compound heterozygotes for Specc1l and Thm1 exhibited a higher penetrance of cleft palate compared to Specc1l heterozygotes alone. Together, these findings reveal a role for SPECC1L in cytoskeletal regulation of ciliogenesis affecting palate development.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":559446,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.948,"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":1460659,"name":"Dana N Thalman","orcid":"0000-0002-4727-5963","position":1,"is_corresponding":false},{"id":1386935,"name":"An J. Tran","orcid":"0009-0005-6360-2433","position":2,"is_corresponding":false},{"id":496740,"name":"Jeremy P. Goering","orcid":null,"position":3,"is_corresponding":false},{"id":496362,"name":"Marta Stetsiv","orcid":"0000-0003-3675-3082","position":4,"is_corresponding":false},{"id":734454,"name":"Michael Moedritzer","orcid":null,"position":5,"is_corresponding":false},{"id":1461270,"name":"Sarah C Wilson","orcid":null,"position":6,"is_corresponding":false},{"id":570553,"name":"Henry H. Wang","orcid":null,"position":7,"is_corresponding":false},{"id":495418,"name":"Pamela V. Tran","orcid":"0000-0003-4619-4376","position":8,"is_corresponding":false},{"id":495896,"name":"Irfan Saadi","orcid":"0000-0002-6250-6651","position":9,"is_corresponding":false},{"id":980811,"name":"Brittany M. Hufft‐Martinez","orcid":"0000-0002-2063-5420","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:55:34.849815Z","pmid":"41278885","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":[]}