H/T to @sciliz for the topic suggestion.
Normal Kidney Development
The first structure to develop in any vertebrate embryo, the pronephros, consists of a single filtering unit and tubule. In some species these structures do not attach to each other; a funnel-shaped structure with finger-like projections "waves" fluid from the site of filtration into the tubule. In some species the pronephros becomes the adult kidney, but in humans and "higher" vertebrates, the pronephros exists only briefly. It induces development of another structure, the mesonephros.
This mesonephros forms multiple filtration units and tubules capable of urinary function, albeit briefly in humans. These ducts become incorporated into the genitourinary system as a more complex metanephric kidney forms. In some animals, such as the zebrafish, the mesonephric kidney is the adult kidney.
Since the zebrafish kidney finishes at the mesonephric stage, it cannot be a perfect model for studying human kidneys; however, it offers many advantages over other models.
For example, the zebrafish embryo is transparent, making it easy to look at things without killing or cutting up the fry:
Zebrafish Embryonic Development (Link to YouTube Video)
Zebrafish breed rapidly and continuously with a generation time of 3 months.
Sequencing of the zebrafish genome facilitates creation of fish labelled with a variety of fluorescent markers, so specific structures can be studied in situ in live critters. Zhou et al labelled glomerular cells with a red marker and tubular structures with green fluorescent protein to make photos of normal nephrogenesis:
Some background nephrogenesis can occur throughout the life of the zebrafish, but it slows down after 6 months of age. They then created a fish with the green marker linked to the zebrafish homolog of Wilm's Tumor 1, a marker of renal progenitor cells. Once again, podocin, a marker of mature glomeruli, drove the red marker. They then treated the fish with gentamicin, a nephrotoxic antibiotic, and showed that after kidney damage the zebrafish grew new nephrons:
So zebrafish can grow new nephrons with genetic markers similar to those of humans in response to kidney damage. Why can't people? And can we learn how zebrafish achieve this feat and make it happen with human cells? Can these nephrogenic cells be used to grow new nephrons in different zebrafish?Using a similar fluorescent tagging technique, Diep et al transplanted progenitor cells from a zebrafish bearing one label to other fish with different labels and demonstrated that these cells would form new kidneys in the recipient fish. These cells worked with progenitor cells in the recipient fish to form the new units:
The Take-Home Message
First, even if you do not love kidneys and urine as much as I do, you must admit that these studies employ cool technology and generate amazing photos. Both of these articles include supplementary photos and videos as well; you should click on over to the web sites and play!
More important, Diep et al show that progenitor cells can be transplanted. Some dormant cells may remain in metanephric kidneys (like we humans have) that we can eventually learn to stimulate to regeneration. Someday we may be able to produce progenitor cells in vitro using stem cells, and then inject them into failing kidneys.
Finally, even with their differences, zebrafish can teach us important things about the development of organs, as well as being cute and hardy pets for our tanks.