Subsequently, new nephrons were identified as arising from basophilic cell clusters that enlarge, form lumens, and eventually elongate into eosinophilic tubules reminiscent of a fully mature nephron. 90 Similarly, the renal tubular epithelium of the medaka kidney exhibited severe damage after exposure to the same nephrotoxin. 91 The initial response to the injury was repair of damaged nephrons, followed

Ion Channel Ligand Library cell line by a second regeneration phase in which numerous mesenchymal clusters and nephrogenic bodies were observed. The appearance of developing nephrons was established as a hallmark for the recapitulation of normal nephron development. 91 In particular, the recent finding that zebrafish undergo neonephrogenesis means that this genetically tractable model can be used as a paradigm to dissect the molecular mechanisms of neonephrogenesis, which have been prohibitive in other species like goldfish. Another appealing avenue for future investigation is the application of chemical genetics to interrogate the role(s) for known Protease Inhibitor Library cell line signaling pathways in the tubular regeneration phase and neonephrogenesis process. Identification

of markers that enable the isolation of scattered renal progenitors will also be crucial, so that the behavior and modulation of these cells can be studied. However, it should be kept in mind that the ability to continually add nephrons to the adult kidney attributable to the presence of renal progenitors is a feature of many teleost fish species. Because continual kidney growth of this nature is O-methylated flavonoid not an attribute of mammals,

the mechanisms of neonephrogenesis may in fact be species-specific. Understanding the differences could also provide tremendous insights about whether mimicking neonephrogenesis in mammals will be possible. A fundamental understanding of zebrafish kidney regeneration may offer insights about how to stimulate regeneration in the setting of other kidney diseases. Although zebrafish, other fish models, and mammals display nephron regeneration, many questions have not been addressed in previous studies. The nature of reparative tubule epithelia, (eg, the contributions of surviving G1 tubular cells and prospective tubular stem cells) is still an issue to resolve and can be performed using genetic fate mapping and lineage analysis. It will likely prove informative to the nephrology field to perform such studies in both zebrafish and mouse models, as a comparative analysis of this regeneration process may reveal crucial similarities and differences. Transgenic injury models in zebrafish have also been developed, and these methods of nephron injury will also provide useful avenues for research. For example, transgenic injury models can target particular cell types and then evaluate regeneration. This has been reported recently for the podocyte cells that comprise the blood filter.