Using zebrafish to study podocyte genesis during kidney development and regeneration

Abstract

SUMMARY During development, vertebrates form a progression of up to three different kidneys that are comprised of functional units termed nephrons. Nephron composition is highly conserved across species, and an increasing appreciation of the similarities between zebrafish and mammalian nephron cell types has positioned the zebrafish as a relevant genetic system for nephrogenesis studies. A key component of the nephron blood filter is a specialized epithelial cell known as the podocyte. Podocyte research is of the utmost importance as a vast majority of renal diseases initiate with the dysfunction or loss of podocytes, resulting in a condition known as proteinuria that causes nephron degeneration and eventually leads to kidney failure. Understanding how podocytes develop during organogenesis may elucidate new ways to promote nephron health by stimulating podocyte replacement in kidney disease patients. In this review, we discuss how the zebrafish model can be used to study kidney development, and how zebrafish research has provided new insights into podocyte lineage specification and differentiation. Further, we discuss the recent discovery of podocyte regeneration in adult zebrafish, and explore how continued basic research using zebrafish can provide important knowledge about podocyte genesis in embryonic and adult environments.

Integration of Cistromic and Transcriptomic Analyses Identifies Nphs2, Mafb, and Magi2 as Wilms’ Tumor 1 Target Genes in Podocyte Differentiation and Maintenance

“…36 Bioinformatic analysis identified single Nphs2 and Magi2 genes and two orthologs for Mafb in the zebrafish genome. Nphs2, 37 mafba, 38 and magi2 were found to be expressed in the glomerular region of the embryonic zebrafish kidney: the pronephros ( Figure 5, A-C).…”

Insights into kidney stem cell development and regeneration using zebrafish

“…However, both of these forms of renal regeneration have now been reported in a variety of other fish that include the zebrafish, catfish, trout, medaka and tilapia [15,62,63,[74][75][76] . Amongst these possible animal models, the advancement of sophisticated genetic tools and methodologies in the zebrafish offers a particularly appealing avenue to delineate the mechanisms of renal regeneration events [77,78] . Indeed, a bevy of recent studies have provided an initial molecular framework to track and decipher such phenomena [78,79] .…”

“…The first segment in the nephron is the blood filter, a structure also known as the renal corpuscle [77] ( Figure 1A). The main components of the corpuscle are the glomerulus, a ball of capillaries that contain circulating blood, is surrounded by a space where the filtrate is collected, known as Bowman's capsule, that enables liquid to be passed into the proximal tubule of the nephron [77] ( Figure 1A).…”

“…The main components of the corpuscle are the glomerulus, a ball of capillaries that contain circulating blood, is surrounded by a space where the filtrate is collected, known as Bowman's capsule, that enables liquid to be passed into the proximal tubule of the nephron [77] ( Figure 1A). The integrity of the blood filter remains relatively constant in humans despite clinical observations that cells from this structure can be detected in the urine of healthy individuals [80] .…”

“…Podocytes are crucial for the effectiveness of the glomerulus because they form an intricate sieve network with specialized extensions known as foot processes that wrap around the capillary bundle [77] . Low numbers of podocyte cells are a common cause and effect of glomerular diseases [80,81] .…”