{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:09:54Z","timestamp":1792786194655,"version":"4.5.0"},"posted":{"date-parts":[[2025,9,17]]},"group-title":"Developmental Biology","reference-count":41,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T00:00:00Z","timestamp":1758067200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["DE030972"],"award-info":[{"award-number":["DE030972"]}]},{"name":"NIH","award":["S10OD028600"],"award-info":[{"award-number":["S10OD028600"]}]},{"name":"NIH","award":["S10OD036207"],"award-info":[{"award-number":["S10OD036207"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Organs and tissues develop in close association with vasculature which transports blood and nutrients and helps to remove waste. The vasculature is composed primarily of endothelial cells, which provide structure, form barriers, and are a source of developmental signals. We recently found that the Mediator, a multiprotein complex, which regulates transcription, was essential for proper vascular development. Here, we investigated the specific role of the Mediator tail subunit Med23 in endothelial cells. Endothelial cell-specific knockout of\n                  <jats:italic>Med23<\/jats:italic>\n                  in mouse embryos using\n                  <jats:italic>Tek-Cre<\/jats:italic>\n                  results in vascular anomalies, including edema, hemorrhage, and mispatterned vasculature, alongside craniofacial defects such as micrognathia and cleft palate. Spatial transcriptomics revealed downregulated expression of key vascular and osteogenic genes in\n                  <jats:italic>Med23<\/jats:italic>\n                  mutants, including\n                  <jats:italic>Vegfr1<\/jats:italic>\n                  and\n                  <jats:italic>Col1a1<\/jats:italic>\n                  , with altered signaling dynamics between endothelial and osteoblast populations. Elevated HIF1\u03b1 expression and reduced VEGF signaling were observed in\n                  <jats:italic>Med23<\/jats:italic>\n                  mutants, suggesting a hypoxia-driven suppression of neural crest cell derived osteoblast maturation. Consistent with this model, pharmacological inhibition of HIF1\u03b1, combined with VEGFA supplementation, rescued craniofacial ossification and extended embryonic viability. These findings reveal a critical role for Med23 in coordinating vascular patterning and intramembranous ossification and highlight distinct hypoxic and angiogenic requirements in craniofacial dermal bone versus axial and appendicular endochondral bone development. Thus, the cranial vasculature and more specifically endothelial cells, play an instructive role in neural crest cell and osteogenic differentiation during cranioskeletal development.\n                <\/jats:p>","DOI":"10.1101\/2025.09.13.676037","type":"posted-content","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T23:35:17Z","timestamp":1758152117000},"source":"Crossref","is-referenced-by-count":2,"title":["Vascular Patterning Shapes Intramembranous Ossification via HIF1\u03b1-VEGF Axis"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9030-3341","authenticated-orcid":false,"given":"Soma","family":"Dash","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, University at Albany, SUNY Albany"},{"name":"RNA Institute, University at Albany, SUNY Albany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6233-8148","authenticated-orcid":false,"given":"Jonathan R.","family":"Rettig","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University at Albany, SUNY Albany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madelaine","family":"Gogol","sequence":"additional","affiliation":[{"name":"Stowers Institute for Medical Research"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2774-3624","authenticated-orcid":false,"given":"Paul A.","family":"Trainor","sequence":"additional","affiliation":[{"name":"Stowers Institute for Medical Research"},{"name":"University of Kansas, Medical Center"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026052618151971000_2025.09.13.676037v2.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02785-6"},{"key":"2026052618151971000_2025.09.13.676037v2.2","doi-asserted-by":"publisher","DOI":"10.1080\/13816810.2024.2447499"},{"key":"2026052618151971000_2025.09.13.676037v2.3","doi-asserted-by":"publisher","DOI":"10.1038\/8792"},{"key":"2026052618151971000_2025.09.13.676037v2.4","doi-asserted-by":"publisher","DOI":"10.1359\/JBMR.050917"},{"issue":"8","key":"2026052618151971000_2025.09.13.676037v2.5","first-page":"1253","article-title":"Inactivation of the beta-catenin gene by Wnt1-Cre-mediated deletion results in dramatic brain malformation and failure of craniofacial development","volume":"128","year":"2001","journal-title":"Dev Camb Engl"},{"key":"2026052618151971000_2025.09.13.676037v2.6","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.240550306"},{"key":"2026052618151971000_2025.09.13.676037v2.7","doi-asserted-by":"publisher","DOI":"10.1177\/154405910708601006"},{"key":"2026052618151971000_2025.09.13.676037v2.8","doi-asserted-by":"publisher","DOI":"10.1177\/0022034520969109"},{"key":"2026052618151971000_2025.09.13.676037v2.9","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.531933"},{"key":"2026052618151971000_2025.09.13.676037v2.10","doi-asserted-by":"publisher","DOI":"10.1242\/dev.126.13.3015"},{"key":"2026052618151971000_2025.09.13.676037v2.11","doi-asserted-by":"publisher","DOI":"10.1038\/s41536-023-00288-1"},{"key":"2026052618151971000_2025.09.13.676037v2.12","doi-asserted-by":"publisher","DOI":"10.1126\/science.1206638"},{"key":"2026052618151971000_2025.09.13.676037v2.13","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.55589"},{"key":"2026052618151971000_2025.09.13.676037v2.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2020.06.020"},{"key":"2026052618151971000_2025.09.13.676037v2.15","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-01-00237.1998"},{"key":"2026052618151971000_2025.09.13.676037v2.16","doi-asserted-by":"publisher","DOI":"10.1093\/ejo\/cjz084"},{"key":"2026052618151971000_2025.09.13.676037v2.17","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-024-06581-z"},{"key":"2026052618151971000_2025.09.13.676037v2.18","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11149"},{"key":"2026052618151971000_2025.09.13.676037v2.19","unstructured":"Maes C , Carmeliet G. 2013. Vascular and Nonvascular Roles of VEGF in Bone Development. In: Madame Curie Bioscience Database [Internet]. Landes Bioscience. [accessed 2025 Aug 9]. https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK6134\/."},{"key":"2026052618151971000_2025.09.13.676037v2.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.04.021"},{"key":"2026052618151971000_2025.09.13.676037v2.21","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M506454200"},{"key":"2026052618151971000_2025.09.13.676037v2.22","doi-asserted-by":"publisher","DOI":"10.1242\/bio.20148078"},{"key":"2026052618151971000_2025.09.13.676037v2.23","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1631288100"},{"key":"2026052618151971000_2025.09.13.676037v2.24","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80259-7"},{"key":"2026052618151971000_2025.09.13.676037v2.25","doi-asserted-by":"publisher","DOI":"10.1086\/346090"},{"key":"2026052618151971000_2025.09.13.676037v2.26","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.23992"},{"key":"2026052618151971000_2025.09.13.676037v2.27","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13601"},{"key":"2026052618151971000_2025.09.13.676037v2.28","unstructured":"Rodriguez Celin M , Steiner RD , Basel D. 1993. COL1A1-and COL1A2-Related Osteogenesis Imperfecta. In: Adam MP , Feldman J , Mirzaa GM , Pagon RA , Wallace SE , Amemiya A , editors. GeneReviews\u00ae. Seattle (WA): University of Washington, Seattle. [accessed 2025 Sept 4]. http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK1295\/."},{"key":"2026052618151971000_2025.09.13.676037v2.29","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.20727"},{"key":"2026052618151971000_2025.09.13.676037v2.30","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-022-02742-1"},{"key":"2026052618151971000_2025.09.13.676037v2.31","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.190144"},{"key":"2026052618151971000_2025.09.13.676037v2.32","first-page":"55","article-title":"Intramembranous osteogenesis and angiogenesis in the chick embryo","volume":"166","year":"1989","journal-title":"J Anat"},{"key":"2026052618151971000_2025.09.13.676037v2.33","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-003-0776-3"},{"key":"2026052618151971000_2025.09.13.676037v2.34","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)47116-5"},{"key":"2026052618151971000_2025.09.13.676037v2.35","doi-asserted-by":"publisher","DOI":"10.1172\/JCI31581"},{"key":"2026052618151971000_2025.09.13.676037v2.36","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2021.10549"},{"key":"2026052618151971000_2025.09.13.676037v2.37","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-022-03332-w"},{"key":"2026052618151971000_2025.09.13.676037v2.38","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(01)00428-2"},{"key":"2026052618151971000_2025.09.13.676037v2.39","doi-asserted-by":"publisher","DOI":"10.1242\/dev.01053"},{"key":"2026052618151971000_2025.09.13.676037v2.40","doi-asserted-by":"publisher","DOI":"10.1242\/dev.129.8.1893"},{"key":"2026052618151971000_2025.09.13.676037v2.41","doi-asserted-by":"publisher","DOI":"10.7150\/thno.45422"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.09.13.676037","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T01:15:30Z","timestamp":1779844530000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.09.13.676037"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,17]]},"references-count":41,"URL":"https:\/\/doi.org\/10.1101\/2025.09.13.676037","relation":{},"subject":[],"published":{"date-parts":[[2025,9,17]]},"subtype":"preprint"}}