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Cell Dev. Biol."],"abstract":"<jats:p>Angiogenesis is a highly coordinated process involving the control of various endothelial cell behaviors. Mechanisms for transcription factor involvement in the regulation of endothelial cell dynamics and angiogenesis have become better understood, however much remains unknown, especially the role of non-DNA binding transcriptional cofactors. Here, we show that Zmiz1, a transcription cofactor, is enriched in the endothelium and critical for embryonic vascular development, postnatal retinal angiogenesis, and pathological angiogenesis in a model of oxygen-induced retinopathy (OIR). In mice, endothelial cell-specific deletion of <jats:italic>Zmiz1<\/jats:italic> during embryogenesis led to lethality due to abnormal angiogenesis and vascular defects. Inducible endothelial cell-specific ablation of <jats:italic>Zmiz1<\/jats:italic> postnatally resulted in impaired retinal vascular outgrowth, decreased vascular density, and increased vessel regression. In addition, angiogenic sprouting in the superficial and deep layers of the retina was markedly reduced. Correspondingly, vascular sprouting in fibrin bead assays was significantly reduced in the absence of Zmiz1, while further <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> evidence also suggested deficits in EC migration. In agreement with the defective sprouting angiogenesis phenotype, gene expression analysis of isolated retinal endothelial cells revealed downregulation of tip-cell enriched genes upon inactivation of <jats:italic>Zmiz1<\/jats:italic>. Lastly, our study suggested that endothelial Zmiz1 is critical for intraretinal revascularization following hypoxia exposure in the OIR model. Taken together, these findings begin to define the previously unspecified role of endothelial Zmiz1 in physiological and pathological angiogenesis.<\/jats:p>","DOI":"10.3389\/fcell.2025.1570587","type":"journal-article","created":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T05:49:31Z","timestamp":1759297771000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Endothelial Zmiz1 modulates developmental angiogenesis in the retina"],"prefix":"10.3389","volume":"13","author":[{"given":"Nehal R.","family":"Patel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shreya A.","family":"Bavishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adella P.","family":"Bartoletti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajan","family":"K C","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avery","family":"Blanks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelsey","family":"Carter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark Y.","family":"Chiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stryder M.","family":"Meadows","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,1]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","DOI":"10.1016\/j.molmet.2022.101621","volume-title":"Zmiz1 is required for mature \u03b2-cell function and mass expansion upon high fat feeding","author":"Alghamdi","year":"2022"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e177819","DOI":"10.1172\/jci.insight.177819","article-title":"Endothelial TDP-43 controls sprouting angiogenesis and vascular barrier integrity, and its deletion triggers neuroinflammation","volume":"9","author":"Arribas","year":"2024","journal-title":"JCI Insight"},{"key":"B3","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1128\/MCB.00771-07","article-title":"The PIAS-like protein Zimp10 is essential for embryonic viability and proper vascular development","volume":"28","author":"Beliakoff","year":"2008","journal-title":"Mol. 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