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Recent advances in elucidating the genetic mechanisms of nephrogenesis using zebrafish.

Cheng CN, Verdun VA, Wingert RA - Cells (2015)

Bottom Line: There is a limited understanding of the genetic mechanisms that establish these discrete nephron cell types during renal development.The zebrafish embryonic kidney serves as a simplified yet conserved vertebrate model to delineate how nephron segments are patterned from renal progenitors.Here, we provide a concise review of recent advances in this emerging field, and discuss how continued research using zebrafish genetics can be applied to gain insights about nephrogenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, Center for Zebrafish Research, and Center for Stem Cells and Regenerative Medicine, University of Notre Dame, Notre Dame, IN 46556, USA. ccheng2@nd.edu.

ABSTRACT
The kidney is comprised of working units known as nephrons, which are epithelial tubules that contain a series of specialized cell types organized into a precise pattern of functionally distinct segment domains. There is a limited understanding of the genetic mechanisms that establish these discrete nephron cell types during renal development. The zebrafish embryonic kidney serves as a simplified yet conserved vertebrate model to delineate how nephron segments are patterned from renal progenitors. Here, we provide a concise review of recent advances in this emerging field, and discuss how continued research using zebrafish genetics can be applied to gain insights about nephrogenesis.

No MeSH data available.


Deficiency of Prkcι/ξ disrupts nephron epithelial polarity. (A) At the 22 ss, actin is mislocalized in Prkcι/ξ deficient embryos, though lumen formation eventually occurs by 36 hpf, accompanied by normal laminin distribution at the basal lamina though Na+/K+ ATPase distribution remains mislocalized at this time point. (B) Summary of phenotypes in Prkcι/ξ deficient embryos compared to wild-type embryos. Abbreviations: hours post fertilization (hpf), mesenchymal to epithelial transition (MET), morpholino (MO) somite stage (ss). [Figure adapted from Reference [57], through terms of the Creative Commons License of the Authors].
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cells-04-00218-f003: Deficiency of Prkcι/ξ disrupts nephron epithelial polarity. (A) At the 22 ss, actin is mislocalized in Prkcι/ξ deficient embryos, though lumen formation eventually occurs by 36 hpf, accompanied by normal laminin distribution at the basal lamina though Na+/K+ ATPase distribution remains mislocalized at this time point. (B) Summary of phenotypes in Prkcι/ξ deficient embryos compared to wild-type embryos. Abbreviations: hours post fertilization (hpf), mesenchymal to epithelial transition (MET), morpholino (MO) somite stage (ss). [Figure adapted from Reference [57], through terms of the Creative Commons License of the Authors].

Mentions: Additionally, it was determined that changes in protein localization lead to the eventual distinction between the apical (Prkcι/ξ+) and basolateral (Na+/K+ ATPase+) regions [57]. Furthermore, the functional significance of these Prkc isoforms in vivo was discovered through single and double morpholino knockdowns in wild-type embryos [57]. In contrast to single Prkc knockdown embryos, double Prkcι/ξ morphants had abnormal localization of actin (Figure 3) and Na+/K+ ATPase, and the protein Ezrin, Radixin, and Moesin (p-ERM) and Prkc proteins were absent from the pronephros, suggesting redundant roles of Prkcι/ξ during nephron tubule polarization [57]. Since previous research has also indicated that renal diseases (e.g., polycystic kidney disease, PKD) are associated with epithelial polarity defects [59], it would be interesting in future studies to further interrogate how renal progenitors are affected by disruptions in Na+/K+ ATPase and p-ERM localization. In addition, investigating whether Prkcι/ξ deficiency, or the combined deficiency of Prkcι/ξ and other polarity regulators, develop cysts or show altered epithelial tubule regeneration could provide useful models to study certain aspects of kidney disease [57,58,59].


Recent advances in elucidating the genetic mechanisms of nephrogenesis using zebrafish.

Cheng CN, Verdun VA, Wingert RA - Cells (2015)

Deficiency of Prkcι/ξ disrupts nephron epithelial polarity. (A) At the 22 ss, actin is mislocalized in Prkcι/ξ deficient embryos, though lumen formation eventually occurs by 36 hpf, accompanied by normal laminin distribution at the basal lamina though Na+/K+ ATPase distribution remains mislocalized at this time point. (B) Summary of phenotypes in Prkcι/ξ deficient embryos compared to wild-type embryos. Abbreviations: hours post fertilization (hpf), mesenchymal to epithelial transition (MET), morpholino (MO) somite stage (ss). [Figure adapted from Reference [57], through terms of the Creative Commons License of the Authors].
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493457&req=5

cells-04-00218-f003: Deficiency of Prkcι/ξ disrupts nephron epithelial polarity. (A) At the 22 ss, actin is mislocalized in Prkcι/ξ deficient embryos, though lumen formation eventually occurs by 36 hpf, accompanied by normal laminin distribution at the basal lamina though Na+/K+ ATPase distribution remains mislocalized at this time point. (B) Summary of phenotypes in Prkcι/ξ deficient embryos compared to wild-type embryos. Abbreviations: hours post fertilization (hpf), mesenchymal to epithelial transition (MET), morpholino (MO) somite stage (ss). [Figure adapted from Reference [57], through terms of the Creative Commons License of the Authors].
Mentions: Additionally, it was determined that changes in protein localization lead to the eventual distinction between the apical (Prkcι/ξ+) and basolateral (Na+/K+ ATPase+) regions [57]. Furthermore, the functional significance of these Prkc isoforms in vivo was discovered through single and double morpholino knockdowns in wild-type embryos [57]. In contrast to single Prkc knockdown embryos, double Prkcι/ξ morphants had abnormal localization of actin (Figure 3) and Na+/K+ ATPase, and the protein Ezrin, Radixin, and Moesin (p-ERM) and Prkc proteins were absent from the pronephros, suggesting redundant roles of Prkcι/ξ during nephron tubule polarization [57]. Since previous research has also indicated that renal diseases (e.g., polycystic kidney disease, PKD) are associated with epithelial polarity defects [59], it would be interesting in future studies to further interrogate how renal progenitors are affected by disruptions in Na+/K+ ATPase and p-ERM localization. In addition, investigating whether Prkcι/ξ deficiency, or the combined deficiency of Prkcι/ξ and other polarity regulators, develop cysts or show altered epithelial tubule regeneration could provide useful models to study certain aspects of kidney disease [57,58,59].

Bottom Line: There is a limited understanding of the genetic mechanisms that establish these discrete nephron cell types during renal development.The zebrafish embryonic kidney serves as a simplified yet conserved vertebrate model to delineate how nephron segments are patterned from renal progenitors.Here, we provide a concise review of recent advances in this emerging field, and discuss how continued research using zebrafish genetics can be applied to gain insights about nephrogenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, Center for Zebrafish Research, and Center for Stem Cells and Regenerative Medicine, University of Notre Dame, Notre Dame, IN 46556, USA. ccheng2@nd.edu.

ABSTRACT
The kidney is comprised of working units known as nephrons, which are epithelial tubules that contain a series of specialized cell types organized into a precise pattern of functionally distinct segment domains. There is a limited understanding of the genetic mechanisms that establish these discrete nephron cell types during renal development. The zebrafish embryonic kidney serves as a simplified yet conserved vertebrate model to delineate how nephron segments are patterned from renal progenitors. Here, we provide a concise review of recent advances in this emerging field, and discuss how continued research using zebrafish genetics can be applied to gain insights about nephrogenesis.

No MeSH data available.