Abstract
Elucidating the gene regulatory networks that control kidney development can provide information about the origins of renal birth defects and kidney disease, as well as insights relevant to the design of clinical interventions for these conditions. The kidney is composed of functional units termed nephrons. Renal malfunction often arises from damage to cells known as podocytes, which are highly specialized epithelial cells that comprise the blood filter, or glomerulus, located on each nephron. Podocytes interact with the vasculature to create an elaborate sieve that collects circulatory fluid, and this filtrate enters the nephron where it is modified to produce urine and balance water homeostasis. Podocytes are an essential cellular component of the glomerular filtration barrier, helping to protect nephrons from the entry of large proteins and circulatory cells. Podocyte loss has catastrophic consequences for renal function and overall health, as podocyte destruction leads to nephron damage and pathological conditions like chronic kidney disease. Despite their importance, there is still a rather limited understanding about the molecular pathways that control podocyte formation. In recent years, however, studies of podocyte development using the zebrafish embryonic kidney, or pronephros, have been an expanding area of nephrology research. Zebrafish form an anatomically simple pronephros comprised of two nephrons that share a single blood filter, and podocyte progenitors can be easily visualized throughout the process of glomerular development. The zebrafish is an especially useful system for studying the mechanisms that are essential for formation of nephron cell types like podocytes due to the high genetic conservation between vertebrate species, including humans. In this review, we discuss how research using the zebrafish has provided new insights into the molecular regulation of the podocyte lineage during kidney ontogeny, complementing contemporary research in other animal models.
Highlights
Kidney structure and function The kidneys are important organs with a set of physiological roles that are essential for life [1]
There were wt1b-expressing podocytes in the wt1a, rbpj, and foxc1a morphants at 24 hpf, they were only abrogated by 36 hpf in the wt1a morphants, and did not express normal levels of other markers characteristic of mature podocytes, such as nephrin and podocalyxin. These results indicate that wt1a plays roles in podocyte maturation and survival
Despite the lack of interaction with NICD3, both these Glutathione Stransferase (GST) tagged proteins could bind the reciprocal protein partner. These results suggest rbpj connects NICD3 with wt1a and foxc1a using protein-protein interactions during podocyte development, the data cannot rule out several distinct protein complexes instead of one large multimeric complex
Summary
Kidney structure and function The kidneys are important organs with a set of physiological roles that are essential for life [1]. Integrity of the glomerulus can be assessed in the zebrafish embryo, which has facilitated the systematic assessment of factors that are essential to form or maintain the filtration barrier through the utilization of gene knockdown tools (like morpholinos) and gain of function studies (such as cDNA over-expression) [16]. Among this gene list is Wt1, which encodes a mammalian zincfinger transcription factor and RNA binding protein that is essential for normal renal development and one of the earliest markers of podocytes in vertebrates [7].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
