{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T17:17:15Z","timestamp":1771262235068,"version":"3.50.1"},"reference-count":38,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82101235"],"award-info":[{"award-number":["82101235"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2025,11,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Our previous study linked a point mutation in\n                    <jats:italic>VWA1<\/jats:italic>\n                    to the development of hemifacial microsomia. This study aims to elucidate the molecular mechanism of\n                    <jats:italic>VWA1<\/jats:italic>\n                    in craniofacial development. We used transgenic technology to generate mice with\n                    <jats:italic>Vwa1<\/jats:italic>\n                    knockdown specifically in cranial neural crest cells (CNCCs). Craniofacial and jawbone development was analyzed using skeletal staining and morphometric measurements. Primary CNCCs were isolated and manipulated via lentiviral vectors. Cellular proliferation, migration, differentiation, and apoptosis were assessed using a suite of in\u00a0vitro assays. RNA\u2010sequencing was employed to identify differentially expressed genes downstream of\n                    <jats:italic>Vwa1<\/jats:italic>\n                    knockdown, and the epigenetic regulation of\n                    <jats:italic>Runx2<\/jats:italic>\n                    by KDM6B was verified via ChIP\u2010qPCR. Conditional deletion of\n                    <jats:italic>Vwa1<\/jats:italic>\n                    in CNCCs resulted in craniofacial hypoplasia, impaired jaw development, and increased CNCC apoptosis in mice. In\u00a0vitro, knockdown of\n                    <jats:italic>Vwa1<\/jats:italic>\n                    inhibited CNCC proliferation and migration, hindered osteogenic and chondrogenic differentiation, and enhanced apoptosis. Mechanistically,\n                    <jats:italic>Vwa1<\/jats:italic>\n                    deletion reduced KDM6B expression. Knockdown of\n                    <jats:italic>Kdm6b<\/jats:italic>\n                    phenocopied the inhibitory effects on CNCC osteogenic differentiation. We demonstrated that KDM6B, a histone demethylase, promotes\n                    <jats:italic>Runx2<\/jats:italic>\n                    transcription by removing H3K27me3 repressive marks from its promoter. Consistent with this,\n                    <jats:italic>Runx2<\/jats:italic>\n                    \u2010deficient mice also developed craniofacial hypoplasia. Importantly, overexpression of\n                    <jats:italic>Kdm6b<\/jats:italic>\n                    or\n                    <jats:italic>Runx2<\/jats:italic>\n                    rescued the osteogenic differentiation defects caused by\n                    <jats:italic>Vwa1<\/jats:italic>\n                    or\n                    <jats:italic>Kdm6b<\/jats:italic>\n                    knockdown, respectively.\n                    <jats:italic>Vwa1<\/jats:italic>\n                    is essential for proper craniofacial development. Its deletion leads to impaired osteogenic differentiation of CNCCs by disrupting KDM6B\u2010mediated epigenetic activation of\n                    <jats:italic>Runx2<\/jats:italic>\n                    , thus establishing a novel regulatory axis in craniofacial morphogenesis.\n                  <\/jats:p>","DOI":"10.1096\/fj.202501160rr","type":"journal-article","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T14:24:39Z","timestamp":1762439079000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>Vwa1<\/i>\n                    Knockdown Causes Craniofacial Defects via Loss of\n                    <i>Kdm6b<\/i>\n                    Function"],"prefix":"10.1096","volume":"39","author":[{"given":"Yibei","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Otolaryngology\u2010Head &amp; Neck Surgery China\u2010Japan Friendship Hospital  Beijing 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