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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.


Model of sim1a functions in nephron segmentation. sim1a is necessary to promote PST and CS formation and inhibit PCT fates during segment patterning in the zebrafish pronephros. These activities occur downstream of RA signaling, which promotes PCT and PST formation and expression of sim1a in these respective renal progenitor domains. Further, RA signaling inhibits sim1a expression in CS progenitors, placing it as a negative regulator upstream of sim1a during establishment of the CS lineage. Abbreviations: corpuscle of Stannius (CS), distal early (DE), distal late (DL), neck (N), podocytes (P), proximal convoluted tubule (PCT), pronephric duct (PD), proximal straight tubule (PST), retinoic acid (RA). [Figure adapted from [45], through terms of the Creative Commons License of the Authors].
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cells-04-00218-f005: Model of sim1a functions in nephron segmentation. sim1a is necessary to promote PST and CS formation and inhibit PCT fates during segment patterning in the zebrafish pronephros. These activities occur downstream of RA signaling, which promotes PCT and PST formation and expression of sim1a in these respective renal progenitor domains. Further, RA signaling inhibits sim1a expression in CS progenitors, placing it as a negative regulator upstream of sim1a during establishment of the CS lineage. Abbreviations: corpuscle of Stannius (CS), distal early (DE), distal late (DL), neck (N), podocytes (P), proximal convoluted tubule (PCT), pronephric duct (PD), proximal straight tubule (PST), retinoic acid (RA). [Figure adapted from [45], through terms of the Creative Commons License of the Authors].

Mentions: In comparison, the loss of sim1a caused different morphant phenotypes with regards to segmentation. In the absence of sim1a, the PCT became expanded while PST and CS populations were completely abrogated [45]. Despite these drastic alterations in the proximal nephron region, the distal segments remained unchanged [45]. Therefore, these data suggest that sim1a is required for PST and CS formation, and could be regulating the PCT/PST by inhibiting PCT cell fate or by stimulating a PST-specific gene program [45] (Figure 5). Furthermore, both mecom and sim1a morphants were characterized by the appearance of pericardial edema and decreased renal clearance functionality as assessed by dextran uptake assays [45,68]. Together, these findings revealed previously unknown roles for mecom and sim1a during the patterning of the nephron and kidney function.


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

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

Model of sim1a functions in nephron segmentation. sim1a is necessary to promote PST and CS formation and inhibit PCT fates during segment patterning in the zebrafish pronephros. These activities occur downstream of RA signaling, which promotes PCT and PST formation and expression of sim1a in these respective renal progenitor domains. Further, RA signaling inhibits sim1a expression in CS progenitors, placing it as a negative regulator upstream of sim1a during establishment of the CS lineage. Abbreviations: corpuscle of Stannius (CS), distal early (DE), distal late (DL), neck (N), podocytes (P), proximal convoluted tubule (PCT), pronephric duct (PD), proximal straight tubule (PST), retinoic acid (RA). [Figure adapted from [45], 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-f005: Model of sim1a functions in nephron segmentation. sim1a is necessary to promote PST and CS formation and inhibit PCT fates during segment patterning in the zebrafish pronephros. These activities occur downstream of RA signaling, which promotes PCT and PST formation and expression of sim1a in these respective renal progenitor domains. Further, RA signaling inhibits sim1a expression in CS progenitors, placing it as a negative regulator upstream of sim1a during establishment of the CS lineage. Abbreviations: corpuscle of Stannius (CS), distal early (DE), distal late (DL), neck (N), podocytes (P), proximal convoluted tubule (PCT), pronephric duct (PD), proximal straight tubule (PST), retinoic acid (RA). [Figure adapted from [45], through terms of the Creative Commons License of the Authors].
Mentions: In comparison, the loss of sim1a caused different morphant phenotypes with regards to segmentation. In the absence of sim1a, the PCT became expanded while PST and CS populations were completely abrogated [45]. Despite these drastic alterations in the proximal nephron region, the distal segments remained unchanged [45]. Therefore, these data suggest that sim1a is required for PST and CS formation, and could be regulating the PCT/PST by inhibiting PCT cell fate or by stimulating a PST-specific gene program [45] (Figure 5). Furthermore, both mecom and sim1a morphants were characterized by the appearance of pericardial edema and decreased renal clearance functionality as assessed by dextran uptake assays [45,68]. Together, these findings revealed previously unknown roles for mecom and sim1a during the patterning of the nephron and kidney function.

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.