Postembryonic Nephrogenesis and Persistence of Six2-Expressing Nephron Progenitor Cells in the Reptilian Kidney

Abstract

New nephron formation (nephrogenesis) ceases in mammals around birth and is completely absent in adults. In contrast, postembryonic nephrogenesis is well documented in the mesonephric kidneys of fishes and amphibians. The transient mesonephros in reptiles (including birds) and mammals is replaced by the metanephros during embryogenesis. Thus, one may speculate that postembryonic nephrogenesis is restricted to the mesonephric kidney. Previous reports have suggested the metanephros of non-avian reptiles (hereafter reptiles) may continually form nephrons throughout life. We investigated the presence of adult nephrogenesis in reptiles by examining adult kidneys from several species including Trachemys scripta, Chrysemys picta, Boa constrictor, Tupinambis tegu, Anolis carolinensis, and Alligator mississipiensis among others. We found that all major reptilian groups (Testudines, Crocodylia, and Squamates) showed the presence of adult nephrogenesis. The total amount of nephrogenesis varied greatly between species with turtles displaying the highest density of nephrogenesis. In contrast, we were unable to detect adult nephrogenesis in monotremes, and in the iguanid A. carolinensis. Nephron progenitor cells express the transcription factor Six2, which in mammals, becomes downregulated as the progenitor cell population is exhausted and nephrogenesis ends. Using the alligator as a model, we were able to detect Six2-positive cap mesenchyme cells in the adult kidney, which spatially correlated with areas of nephrogenesis. These results suggest that the metanephric kidney of reptiles has maintained the ability to continually grow new nephrons during postembryonic life, a process lost early in mammalian evolution, likely due to the persistence of a Six2-expressing progenitor cell population.

Tumor-free elongation of mammalian nephrogenesis by excess fetal GDNF

“…Epidemiological studies indicate that those born with a higher nephron count are better protected against kidney disease and have a lower risk for hypertension and cardiovascular diseases later in life (Starr & Hingorani, 2018). Neonephrogenesis, the formation of new nephrons after the cessation of the fetal nephrogenic program observed in some vertebrates, is not an inherent feature of mammalian kidneys (Camarata, Howard et al, 2016). When diseased or injured, mammalian nephrons permanently lose their function as the adult kidney shows very limited regeneration, and instead responds to insult by compensatory growth through glomeruli and tubular hypertrophy (Chawla & Kimmel, 2012, Romagnani et al, 2013, Westland, Schreuder et al, 2014.…”

Comparative morphology and allometry of select extant cryptodiran turtle kidneys

“…It has been reported that the lobed reptile kidney has a specific organization with renal corpuscles lining the center of each lobe and the collecting ducts positioned at right angles to the long axis of the kidney (Braun et al 2011). This organization has been found in the American alligator (Alligator mississippiensis), however, such tissue organization has not detected thus far in other reptiles (Moore et al 2009;Camarata et al 2016). Future studies will be aimed to correlate external morphology with histological organization…”

“…However, there is little detailed description of comparative renal morphology in turtles. Our previous work detailing the appearance of continual nephrogenesis in reptiles hinted at distinct variations in kidney morphology and tissue architecture (Camarata et al 2016). The primary objective of this investigation is to describe, in detail, the comparative kidney morphology using imaging and allometry among select species of the turtle families Chelydridae, Emydidae, Kinosternidae, and Trionychidae.…”

mTOR Signaling at the Crossroad between Metazoan Regeneration and Human Diseases

“…In contrast, formation of nephrons de novo has been reported in the adult little skate, Leucoraja erinacea, an elasmobranch cartilaginous fish, after partial nephrectomy [70]. Similarly, in the adult zebrafish kidney and using transplantation experiments, a small group of cells were discovered as able to form functional nephrons [71,73]. In the skate, histological analysis revealed an enhancement of nephron growth in the nephrogenic zone, both in the remnant tissue and in the contralateral kidney.…”

“…The tubule is where diverse molecules are secreted and reabsorbed. Adult mammals cannot form new nephrons contrary to cartilaginous fish, bony fish or certain amphibians [70][71][72][73]. However, cellular mechanisms can contribute to the reparation of mammalian renal structures.…”