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Over the first few days after birth, growth slows and the murine thymus switches from fetal to adult morphology and function; little is known about the cues driving this dramatic transition. In this study, we show for the first time (to our knowledge) the critical role of vascular endothelial growth factor (VEGF) on thymic morphogenesis beyond its well-known role in angiogenesis. During a brief window a few days after birth, VEGF inhibition induced rapid and profound remodeling of the endothelial, mesenchymal and epithelial thymic stromal compartments, mimicking changes seen during early adult maturation. Rapid transcriptional changes were seen in each compartment after VEGF inhibition, including genes involved in migration, chemotaxis, and cell adhesion as well as induction of a proinflammatory and proadipogenic signature in endothelium, pericytes, and mesenchyme. Thymocyte numbers fell subsequent to the stromal changes. Expression patterns and functional blockade of the receptors VEGFR2 and NRP1 demonstrated that VEGF mediates its pleiotropic effects through distinct receptors on each microenvironmental compartment of the developing mouse thymus.<\/jats:p>","DOI":"10.4049\/jimmunol.1901519","type":"journal-article","created":{"date-parts":[[2020,9,28]],"date-time":"2020-09-28T20:00:20Z","timestamp":1601323220000},"page":"2423-2436","source":"Crossref","is-referenced-by-count":2,"title":["Pleiotropic Roles of VEGF in the Microenvironment of the Developing Thymus"],"prefix":"10.1093","volume":"205","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1168-069X","authenticated-orcid":false,"given":"Stephanie C","family":"de Barros","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of California Los Angeles , Los Angeles, CA 90095"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3576-7482","authenticated-orcid":false,"given":"Batul T","family":"Suterwala","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of California Los Angeles , Los Angeles, CA 90095"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chongbin","family":"He","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of California Los Angeles , Los Angeles, CA 90095"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shundi","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of California Los Angeles , Los Angeles, CA 90095"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brent","family":"Chick","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of California Los Angeles , Los Angeles, CA 90095"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Garrett K","family":"Blumberg","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of California Los Angeles , Los Angeles, CA 90095"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2309-4858","authenticated-orcid":false,"given":"Kenneth","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of California Los Angeles , Los Angeles, CA 90095"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sam","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of California Los Angeles , Los Angeles, CA 90095"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuhua","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of California Los Angeles , Los Angeles, CA 90095"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of General Internal Medicine and Health Services Research, University of California Los Angeles , Los Angeles, CA 90095"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7347-3330","authenticated-orcid":false,"given":"David","family":"Casero","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of California Los Angeles , Los Angeles, CA 90095"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gay M","family":"Crooks","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of California Los Angeles , Los Angeles, CA 90095"},{"name":"Department of Pediatrics, University of California Los Angeles , Los Angeles, CA 90095"},{"name":"Broad Stem Cell Research Center, University of California Los Angeles , Los Angeles, CA 90095"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,11,1]]},"reference":[{"key":"2025030417505494500_r1","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/nri1781","article-title":"Journey through the thymus: stromal guides for T-cell development and selection","volume":"6","author":"Takahama","year":"2006","journal-title":"Nat. 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