{"doi":"10.1242/dev.204875","title":"Differential regulation of coronal and lambdoid suture patency by PTHLH and HHIP activity in mice","abstract":"Craniofacial development depends on the formation of fibrous joints, or sutures, between skull bones. Premature fusion of sutures, or craniosynostosis, is a common human pathology. Ectopic Hedgehog (HH) signaling is one cause of craniosynostosis. Hhip encodes an inhibitor of HH ligands, and we previously identified coronal suture dysgenesis in embryonic Hhip-/- mice, in which suture mesenchyme was depleted between closely opposed but unfused osteogenic fronts at E18.5. Here, we report that the lambdoid suture fuses in Hhip-/- mice by E18.5. RNA-seq analysis of the Hhip-/- coronal and lambdoid sutures show that HH target gene expression, including Pthlh, is upregulated. Paradoxically, expression of Ihh is downregulated. We hypothesized that PTHLH, a negative regulator of Ihh expression, may reduce HH signaling to promote coronal suture patency and prevent fusion of the Hhip-/- coronal suture. We generated Hhip-/-;Pthlh-/- embryos and found that coronal sutures are fusing by E18.5. Our results reveal a previously undescribed role for Pthlh in suture development and demonstrate suture-specific roles for HH inhibitors in maintaining suture patency.","journal":"Development","year":2025,"id":547162,"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":0.9539,"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":672674,"name":"Susan M. Motch Perrine","orcid":"0000-0003-3412-221X","position":1,"is_corresponding":false},{"id":1439590,"name":"Qingyang Li","orcid":"0000-0003-1560-7270","position":2,"is_corresponding":false},{"id":598794,"name":"Joan T. Richtsmeier","orcid":"0000-0002-0239-5822","position":3,"is_corresponding":false},{"id":308809,"name":"Ethylin Wang Jabs","orcid":"0000-0001-8983-5466","position":4,"is_corresponding":false},{"id":21492,"name":"Harm van Bakel","orcid":"0000-0002-1376-6916","position":5,"is_corresponding":false},{"id":308802,"name":"Greg Holmes","orcid":"0000-0003-0717-6722","position":6,"is_corresponding":false},{"id":672673,"name":"Madrikha Saturne","orcid":"0000-0001-6677-5675","position":0,"is_corresponding":true}],"reference_count":89,"raw_metadata":null,"created_at":"2026-07-19T02:53:41.314800Z","pmid":"41000054","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":[]}