Journal of Cell Science & Therapy
Open Access

Modeling renal progenitor development using the zebrafish kidney

5^th World Congress on Cell & Stem Cell Research

March 23-25, 2015 DoubleTree by Hilton Chicago - North Shore, USA

Gary F Gerlach and Rebecca A Wingert

Scientific Tracks Abstracts: J Cell Sci Ther

Abstract :

Chronic kidney disease (CKD) affects 300 million people world-wide, representing the 12th leading cause of death. Understanding how nephrons, the simplest functional unit of the kidney, develop from renal progenitors can lend insight into the processes that go awry during disease. The zebrafishpronephros provides an excellent in vivo system to study the mechanisms of vertebrate nephrogenesis. When and how renal progenitors in the zebrafish embryo undergo tubulogenesis to form nephrons is poorly understood, but is known to involve a mesenchymal to epithelial transition (MET) and the acquisition of polarity. We determined the precise timing of these events in pronephros tubulogenesis. As the ternary polarity complex is an essential regulator of epithelial cell polarity across tissues, we performed gene knockdown studies to assess the roles of the related factors atypical protein kinase C iota and zeta (prkcι, prkcζ). We found that prkcιand prkcζ serve partially redundant functions to establish pronephros tubule epithelium polarity. Further, the loss of prkcιor the combined knockdown of prkcι/ζ disrupted proximal tubule morphogenesis and podocyte migration due to cardiac defects that prevented normal fluid flow to the kidney. Surprisingly, tubule cells in prkcι/ζmorphants displayed ectopic expression of the transcription factor pax2a and the podocyte-associated genes wt1a, wt1b, and podxl, suggesting that prkcι/ζ are needed to maintain renal epithelial identity. Interestingly, knockdown of pax2a, but not wt1a, was sufficient to rescue ectopic tubule gene expression in prkcι/ζmorphants. These data suggest a model in which the redundant activities of prkcι and prkcζ are essential to establish tubule epithelial polarity and also serve to maintain proper epithelial cell type identity in the tubule by inhibiting pax2a expression. These studies provide a valuable foundation for further analysis of MET during nephrogenesis, and have implications for understanding the pathways that affect renalprogenitors during kidney development, disease, and regeneration.