{"doi":"10.1016/j.jmccpl.2025.100458","title":"Isoform switch of T-cell factor7L2 during mouse heart development","abstract":"Canonical WNT signaling plays critical, often opposing roles in heart development and disease, but its context-dependent mechanisms remain unclear. We hypothesized that alternative splicing of Tcf7l2, a key nuclear partner of β-catenin, contributes to WNT signaling specificity in the heart. To investigate this, we cloned and sequenced 53 Tcf7l2 transcripts in ventricular tissues from embryonic day 17.5 (E17.5, 24/53) and postnatal day 8 (P8, 29/53) mice, identifying 32 distinct isoforms. Among 18 potential exons, exons 6 and 17 were absent, and over 80 % of transcripts lacked exon 4. Alternative splicing was prominent in the C-terminal exons (14, 15, and 16), with exon 14 inclusion significantly higher in P8 hearts (64.3 %) than E17.5 hearts (34.8 %). Variations in exon 15 and 16 combinations, along with reading frame shifts caused by the adenine insertion and deletion (indel) near the beginning of exon 18, affected C-terminal structures, altering the presence of the E-tail, C-clamp, and CtBP-binding motifs. Notably, exon 14 insertion introduced a redox-switch domain spanning the NLS and C-clamp regions in E and S isoforms, while adenine indels altered isoform lengths, driving transitions between E, S, and M isoforms. RT-PCR validation across multiple developmental stages confirmed these splicing patterns. Our findings suggest that a postnatal redox-sensitive isoform switch in Tcf7l2 modulates WNT signaling, potentially influencing cardiomyocyte maturation during the transition from proliferation to hypertrophy.","journal":"Journal of Molecular and Cellular Cardiology Plus","year":2025,"id":566595,"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":0.954,"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":1470649,"name":"Xiao Lu","orcid":"0000-0002-8539-1375","position":1,"is_corresponding":false},{"id":1470650,"name":"Yuyong Xu","orcid":"0000-0002-6403-714X","position":2,"is_corresponding":false},{"id":292522,"name":"Haodong Xu","orcid":"0000-0003-2086-3893","position":3,"is_corresponding":false},{"id":377042,"name":"Faqian Li","orcid":"0000-0002-9954-095X","position":4,"is_corresponding":false},{"id":917194,"name":"Bo Ye","orcid":"0000-0002-1728-6506","position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:56:40.491968Z","pmid":"40519869","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":[]}