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Ablation of the epithelial‐specific splicing factor Esrp1 results in ureteric branching defects and reduced nephron number
Author(s) -
Bebee Thomas W.,
SimsLucas Sunder,
Park Juw Won,
Bushnell Daniel,
Cieply Benjamin,
Xing Yi,
Bates Carlton M.,
Carstens Russ P.
Publication year - 2016
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.24431
Subject(s) - ureteric bud , kidney development , biology , nephron , mesenchyme , rna splicing , alternative splicing , kidney , microbiology and biotechnology , kidney disease , medicine , endocrinology , embryonic stem cell , messenger rna , rna , embryo , genetics , gene
Background: 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‐specific splicing regulator Esrp1 is required for expression of Fgfr2‐IIIb and other epithelial‐specific splice variants. Our objective was to determine whether Esrp1 is required for normal kidney development. Results: 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‐dimensional imaging showed that embryonic Esrp1 knockout (KO) kidneys had fewer ureteric tips and reduced nephron numbers. Analysis of alternative splicing in Esrp‐null ureteric epithelial cells by RNA‐Seq confirmed a splicing switch in Fgfr2 as well as numerous other transcripts. Conclusions: Our findings reveal that Esrp1‐regulated 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. Developmental Dynamics 245:991–1000, 2016 . © 2016 The Authors. Developmental Dynamics published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.