{"doi":"10.1101/2023.07.05.547801","title":"Survival and Developmental Progression of Unselected Thymocytes in the Absence of the T Cell Adaptor Gads","abstract":"Abstract Thymic development is tightly regulated by TCR signaling via the immune adaptors SLP-76 and LAT. Gads bridges the TCR-induced recruitment of SLP-76 to LAT; yet is not absolutely required for thymic progression. To better identify Gads-dependent developmental transitions, we performed tamoxifen-induced ablation of Gads (Gads iKO ), accompanied by expression of tdTomato, and compared the development of Gads-expressing (Tom − ) and - ablated (Tom + ) thymocytes within the same mouse. The frequency of Gads iKO (Tom + ) thymocytes decreased at β-selection and positive selection, confirming the Gads-dependence of these junctures; nevertheless, we observed small populations of positively-selected Gads iKO SP thymocytes. Consistent with a signaling defect, expression of CD5 was strongly impaired at the β-selection checkpoint and within the DP compartment; moreover, Gads iKO DP thymocytes exhibited reduced TCR-induced calcium flux. Surprisingly, MHC-non-responding (CD5 − ) Gads iKO DP thymocytes exhibited reduced death by neglect; instead, aberrant populations of CD5 − Gads iKO thymocytes progressed as far as the CD4 SP compartment, while lacking key characteristics of positively selected thymocytes. In an experimentally-induced model of death by neglect triggered by CD8 crosslinking, Gads was required for the preferential apoptosis of CD5 lo DP thymocytes. Our results suggest that Gads promotes passage through TCR-driven developmental checkpoints while also promoting the death by neglect of unselected thymocytes.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":409324,"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":0.9522,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1189293,"name":"Manal Marzouk","orcid":null,"position":1,"is_corresponding":false},{"id":479517,"name":"Enas Hallumi","orcid":"0000-0003-3702-1940","position":2,"is_corresponding":false},{"id":1189294,"name":"Naama Klopstock","orcid":null,"position":3,"is_corresponding":false},{"id":479533,"name":"Deborah Yablonski","orcid":"0000-0003-2979-0440","position":4,"is_corresponding":false},{"id":1189292,"name":"Rose Shalah","orcid":null,"position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-19T01:21:27.199694Z","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":[]}