{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T18:19:18Z","timestamp":1791051558189,"version":"4.1.0"},"reference-count":42,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2017,1,1]],"date-time":"2017-01-01T00:00:00Z","timestamp":1483228800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK099478"],"award-info":[{"award-number":["R01DK099478"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK074398"],"award-info":[{"award-number":["R01DK074398"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK091530"],"award-info":[{"award-number":["R01DK091530"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["P30DK079328"],"award-info":[{"award-number":["P30DK079328"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000912","name":"March of Dimes Foundation","doi-asserted-by":"publisher","award":["5-FY13-201"],"award-info":[{"award-number":["5-FY13-201"]}],"id":[{"id":"10.13039\/100000912","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>In many types of tubules, continuity of the lumen is paramount to tubular function, yet how tubules generate lumen continuity in vivo is not known. We recently found the F-actin binding protein Afadin is required for lumen continuity in developing renal tubules, though its mechanism of action remains unknown. Here we demonstrate Afadin is required for lumen continuity by orienting the mitotic spindle during cell division. Using an in vitro 3D cyst model, we find Afadin localizes to the cell cortex adjacent to the spindle poles and orients the mitotic spindle. In tubules, cell division may be oriented relative to two axes, longitudinal and apical-basal. Unexpectedly, in vivo examination of early stage developing nephron tubules reveals cell division is not oriented in the longitudinal (or planar polarized) axis. However, cell division is oriented perpendicular to the apical-basal axis. Absence of Afadin in vivo leads to misorientation of apical-basal cell division in nephron tubules. Together these results support a model whereby Afadin determines lumen placement by directing apical-basal spindle orientation, which generates a continuous lumen and normal tubule morphogenesis.<\/jats:p>","DOI":"10.1242\/dev.148908","type":"journal-article","created":{"date-parts":[[2017,9,1]],"date-time":"2017-09-01T00:10:25Z","timestamp":1504224625000},"source":"Crossref","is-referenced-by-count":18,"title":["Developing renal tubules orient cell division via Afadin to position the tubule lumen"],"prefix":"10.1242","author":[{"given":"Lei","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, Texas, 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6495-2316","authenticated-orcid":false,"given":"Zhufeng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, Texas, 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1770-8112","authenticated-orcid":false,"given":"Chitkale","family":"Hiremath","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, Texas, 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan E.","family":"Zimmerman","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, Texas, 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blake","family":"Long","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, Texas, 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul R.","family":"Brakeman","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics, University of California, San Francisco, California, 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith E.","family":"Mostov","sequence":"additional","affiliation":[{"name":"Anatomy, University of California, San Francisco, California, 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Bryant","sequence":"additional","affiliation":[{"name":"Cancer Research UK, Beatson Institute, and Institute of Cancer Sciences, University of Glasgow, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Luby-Phelps","sequence":"additional","affiliation":[{"name":"Department of Cell biology, University of Texas Southwestern Medical Center, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0612-4664","authenticated-orcid":false,"given":"Denise K.","family":"Marciano","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, Texas, 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2017,1,1]]},"reference":[{"key":"2021042609021519300_DEV148908C1","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1002\/embj.201385946","article-title":"EGFR controls IQGAP basolateral membrane localization and mitotic spindle orientation during epithelial morphogenesis","volume":"33","author":"Ba\u00f1\u00f3n-Rodr\u00edguez","year":"2014","journal-title":"EMBO J."},{"key":"2021042609021519300_DEV148908C2","doi-asserted-by":"publisher","first-page":"9064","DOI":"10.1073\/pnas.97.16.9064","article-title":"The junctional multidomain protein AF-6 is a binding partner of the Rap1A GTPase and associates with the actin cytoskeletal regulator profilin","volume":"97","author":"Boettner","year":"2000","journal-title":"Proc. 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