{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T20:06:40Z","timestamp":1786133200678,"version":"build-2736575974"},"reference-count":56,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01HLI125811"],"award-info":[{"award-number":["1R01HLI125811"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01EY025979-01"],"award-info":[{"award-number":["1R01EY025979-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 EY026878"],"award-info":[{"award-number":["P30 EY026878"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001674","name":"Fondation Leducq","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001674","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:sec>\n                    <jats:title>Significance Statement<\/jats:title>\n                    <jats:p>\n                      Slit2 is a secreted ligand for Robo1 and Robo2 receptors.\n                      <jats:italic toggle=\"yes\">Slit2<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Robo2<\/jats:italic>\n                      mutations lead to congenital abnormalities of the kidney and ureteric tract, underscoring the requirement of this signaling pathway for kidney development. Previous studies in global mouse knockouts demonstrated that Slit2-Robo2 signaling restricts ureteric epithelium budding. Temporally inducible Slit2 and Robo deletions reveal a novel role of Slit2-Robo signaling in glomerular vascularization in mice. Only the glomerular endothelium, but no other renal endothelial compartment, responded to Slit2 via Robo receptors. Postnatally induced\n                      <jats:italic toggle=\"yes\">Slit2<\/jats:italic>\n                      gene deletion or a Slit2 ligand trap inhibited glomerular vascularization by reducing endothelial cell proliferation and migration, identifying Slit2 as a driver of glomerular angiogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Kidney function requires continuous blood filtration by glomerular capillaries. Disruption of glomerular vascular development or maintenance contributes to the pathogenesis of kidney diseases, but the signaling events regulating renal endothelium development remain incompletely understood. Here, we discovered a novel role of Slit2-Robo signaling in glomerular vascularization. Slit2 is a secreted polypeptide that binds to transmembrane Robo receptors and regulates axon guidance as well as ureteric bud branching and angiogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We performed Slit2-alkaline phosphatase binding to kidney cryosections from mice with or without tamoxifen-inducible\n                      <jats:italic toggle=\"yes\">Slit2<\/jats:italic>\n                      or\n                      <jats:italic toggle=\"yes\">Robo1 and -2<\/jats:italic>\n                      deletions, and we characterized the phenotypes using immunohistochemistry, electron microscopy, and functional intravenous dye perfusion analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Only the glomerular endothelium, but no other renal endothelial compartment, responded to Slit2 in the developing kidney vasculature. Induced\n                      <jats:italic toggle=\"yes\">Slit2<\/jats:italic>\n                      gene deletion or Slit2 ligand trap at birth affected nephrogenesis and inhibited vascularization of developing glomeruli by reducing endothelial proliferation and migration, leading to defective cortical glomerular perfusion and abnormal podocyte differentiation. Global and endothelial-specific Robo deletion showed that both endothelial and epithelial Robo receptors contributed to glomerular vascularization.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study provides new insights into the signaling pathways involved in glomerular vascular development and identifies Slit2 as a potential tool to enhance glomerular angiogenesis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.2020111640","type":"journal-article","created":{"date-parts":[[2021,8,2]],"date-time":"2021-08-02T18:05:28Z","timestamp":1627927528000},"page":"2255-2272","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":18,"title":["Slit2-Robo Signaling Promotes Glomerular Vascularization and Nephron Development"],"prefix":"10.1681","volume":"32","author":[{"given":"Jinyu","family":"Li","sequence":"first","affiliation":[{"name":"Department of Cellular and Molecular Physiology, Yale University Medical School, New Haven, Connecticut"},{"name":"Cardiovascular Research Center, Department of Internal Medicine, Yale University, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3318-4697","authenticated-orcid":false,"given":"Luiz Henrique","family":"Geraldo","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Center, Department of Internal Medicine, Yale University, New Haven, Connecticut"},{"name":"Universit\u00e9 de Paris, Paris Cardiovascular Research Center, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U907, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3829-2577","authenticated-orcid":false,"given":"Alexandre","family":"Dubrac","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Center, Department of Internal Medicine, Yale University, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgia","family":"Zarkada","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Center, Department of Internal Medicine, Yale University, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Eichmann","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Physiology, Yale University Medical School, New Haven, Connecticut"},{"name":"Cardiovascular Research Center, Department of Internal Medicine, Yale University, New Haven, Connecticut"},{"name":"Universit\u00e9 de Paris, Paris Cardiovascular Research Center, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U907, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2021,9]]},"reference":[{"key":"B1-20240826","doi-asserted-by":"crossref","first-page":"5705","DOI":"10.1038\/s41467-019-12872-5","article-title":"Molecular determinants of nephron vascular specialization in the kidney","volume":"10","author":"Barry","year":"2019","journal-title":"Nat Commun"},{"key":"B2-20240826","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1007\/s10456-018-9612-y","article-title":"Spatiotemporal heterogeneity and patterning of developing renal blood vessels","volume":"21","author":"Daniel","year":"2018","journal-title":"Angiogenesis"},{"key":"B3-20240826","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.semcdb.2014.08.002","article-title":"Patterning the renal vascular 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