{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T14:16:06Z","timestamp":1761920166732,"version":"build-2065373602"},"reference-count":49,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2016,7,28]],"date-time":"2016-07-28T00:00:00Z","timestamp":1469664000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"TWB","award":["T32-DK700638 and F32-DK098917"],"award-info":[{"award-number":["T32-DK700638 and F32-DK098917"]}]},{"name":"SSL","award":["K01-DK096996"],"award-info":[{"award-number":["K01-DK096996"]}]},{"name":"CMB","award":["R01-DK095748"],"award-info":[{"award-number":["R01-DK095748"]}]},{"name":"Pittsburgh O'Brien Center P30","award":["DK079307"],"award-info":[{"award-number":["DK079307"]}]},{"name":"RPC","award":["R01-GM088809 and R56-DK097257"],"award-info":[{"award-number":["R01-GM088809 and R56-DK097257"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Developmental Dynamics"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:sec><jats:title>Background:<\/jats:title><jats:p>Abnormalities in ureteric bud (UB) branching morphogenesis lead to congenital anomalies of the kidney and reduced nephron numbers associated with chronic kidney disease (CKD) and hypertension. Previous studies showed that the epithelial fibroblast growth factor receptor 2 (Fgfr2) IIIb splice variant supports ureteric morphogenesis in response to ligands from the metanephric mesenchyme during renal organogenesis. The epithelial\u2010specific splicing regulator Esrp1 is required for expression of Fgfr2\u2010IIIb and other epithelial\u2010specific splice variants. Our objective was to determine whether Esrp1 is required for normal kidney development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p>Ablation of Esrp1 in mice, alone or together with its paralog Esrp2, was associated with reduced kidney size and increased incidence of renal aplasia. Three\u2010dimensional imaging showed that embryonic Esrp1 knockout (KO) kidneys had fewer ureteric tips and reduced nephron numbers. Analysis of alternative splicing in Esrp\u2010null ureteric epithelial cells by RNA\u2010Seq confirmed a splicing switch in Fgfr2 as well as numerous other transcripts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions:<\/jats:title><jats:p>Our findings reveal that Esrp1\u2010regulated splicing in ureteric epithelial cells plays an important role in renal development. Defects in Esrp1 KO kidneys likely reflect reduced and\/or absent ureteric branching, leading to decreased nephron induction secondary to incorrect Fgfr2 splicing and other splicing alterations. <jats:italic>Developmental Dynamics 245:991\u20131000, 2016<\/jats:italic>. \u00a9 2016 The Authors. Developmental Dynamics published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.<\/jats:p><\/jats:sec>","DOI":"10.1002\/dvdy.24431","type":"journal-article","created":{"date-parts":[[2016,7,12]],"date-time":"2016-07-12T09:24:30Z","timestamp":1468315470000},"page":"991-1000","source":"Crossref","is-referenced-by-count":22,"title":["Ablation of the epithelial\u2010specific splicing factor Esrp1 results in ureteric branching defects and reduced nephron number"],"prefix":"10.1002","volume":"245","author":[{"given":"Thomas W.","family":"Bebee","sequence":"first","affiliation":[{"name":"Department of Medicine (Renal Division), Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sunder","family":"Sims\u2010Lucas","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Pediatrics University of Pittsburgh School of Medicine Pittsburgh Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juw Won","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Computer Engineering and Computer Science, KBRIN Bioinformatics Core University of Louisville Louisville Kentucky"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Bushnell","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Pediatrics University of Pittsburgh School of Medicine Pittsburgh Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Cieply","sequence":"additional","affiliation":[{"name":"Department of Medicine (Renal Division), Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics 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