Expression of collagen type IV in human kidney during prenatal development

Background / Aim. Type IV collagen belongs to the group of non-fibrillar collagens and is an important component of the basement membranes where it accounts for approximately 50% of its structural elements. The aim of the paper was to describe the expression and distribution of collagen type IV in embryonic and fetal metanephric kidney, and to determine the volume density of collagen type IV in kidney tissue in each trimester of development. Methods. The material consisted of 19 human embryos/fetuses, in the gestational age from 8th to 37th week. Kidney tissue specimens were routinely processed to paraffin molds and stained with hematoxylin and eosin and immunohistochemically using polyclonal anti-collagen IV antibody. Stained slides were examined using light microscope and images of the selected areas, under different lens magnification were captured with digital camera. Volume density of collagen type IV was determined by using ImageJ 1.48v and a plugin of the software which inserted a grid system with 336 points. For the data comparison One-Way Analysis of Variance was used. Results. Strong collagen IV immunopositivity was seen in all specimens, with a distribution in the basement membranes of urinary bud, parietal leaf of Bowman?s capsule, glomerular basement membrane, basement membrane of interstitial blood vessels, and basement membranes of nephron tubules and collecting ducts. No statistically significant difference in the volume density of type IV collagen was found between the different trimesters of development. Conclusion. The synthesis and secretion of collagen type IV simultaneously follows the development of nephron structures, collecting system and blood vessels. The volume density of collagen type IV remains constant throughout all the trimesters of metanephric kidney development, indicating that it plays a crucial role in normal development of nephron and collecting system structures, as well as in maintaining the normal kidney function.

Comparative morphology and allometry of select extant cryptodiran turtle kidneys

Reptile, avian, and mammalian species all possess a metanephric kidney to maintain fluid homeostasis. The physiology of the kidney is intimately related to tissue organization and gross morphology, which is dependent upon organ size, animal habitat, and body plan. Reptiles have significant variations in body plan and as a result have differences in visceral organ placement and morphology. One organ that appears to show great morphological variation is the reptilian kidney found in Crocodylia, Testudines, and Squamata (Sauria and Ophidia). However, limited research has been conducted to evaluate and compare kidney morphology in reptiles and more specifically, in turtles. Here we have examined multiple cryptodiran turtle species from the families Chelydridae, Emydidae, Kinosternidae, and Trionychidae. Detailed descriptions of kidney morphology along with comparative allometry are provided. Significant differences in external renal morphology were found between and within turtle families as well as differences in scaling of kidney mass with body mass. Our study provides a foundation for understanding differences in organ development and tissue architecture as well as potential differences in physiology.

Stromal prorenin receptor is critical for normal kidney development

Formation of the metanephric kidney requires coordinated interaction among the stroma, ureteric bud, and cap mesenchyme. The transcription factor Foxd1, a specific marker of renal stromal cells, is critical for normal kidney development. The prorenin receptor (PRR), a receptor for renin and prorenin, is also an accessory subunit of the vacuolar proton pump V-ATPase. Global loss of PRR is embryonically lethal in mice, indicating an essential role of the PRR in embryonic development. Here, we report that conditional deletion of the PRR in Foxd1+ stromal progenitors in mice ( cKO) results in neonatal mortality. The kidneys of surviving mice show reduced expression of stromal markers Foxd1 and Meis1 and a marked decrease in arterial and arteriolar development with the subsequent decreased number of glomeruli, expansion of Six2+ nephron progenitors, and delay in nephron differentiation. Intrarenal arteries and arterioles in cKO mice were fewer and thinner and showed a marked decrease in the expression of renin, suggesting a central role for the PRR in the development of renin-expressing cells, which in turn are essential for the proper formation of the renal arterial tree. We conclude that stromal PRR is crucial for the appropriate differentiation of the renal arterial tree, which in turn may restrict excessive expansion of nephron progenitors to promote a coordinated and proper morphogenesis of the nephrovascular structures of the mammalian kidney.

Reciprocal Spatiotemporally Controlled Apoptosis Regulates Wolffian Duct Cloaca Fusion

The epithelial Wolffian duct (WD) inserts into the cloaca (primitive bladder) before metanephric kidney development, thereby establishing the initial plumbing for eventual joining of the ureters and bladder. Defects in this process cause common anomalies in the spectrum of congenital anomalies of the kidney and urinary tract (CAKUT). However, developmental, cellular, and molecular mechanisms of WD-cloaca fusion are poorly understood. Through systematic analysis of early WD tip development in mice, we discovered that a novel process of spatiotemporally regulated apoptosis in WD and cloaca was necessary for WD-cloaca fusion. Aberrant RET tyrosine kinase signaling through tyrosine (Y) 1062, to which PI3K- or ERK-activating proteins dock, or Y1015, to which PLCγ docks, has been shown to cause CAKUT-like defects. Cloacal apoptosis did not occur in RetY1062F mutants, in which WDs did not reach the cloaca, or in RetY1015F mutants, in which WD tips reached the cloaca but did not fuse. Moreover, inhibition of ERK or apoptosis prevented WD-cloaca fusion in cultures, and WD-specific genetic deletion of YAP attenuated cloacal apoptosis and WD-cloacal fusion in vivo. Thus, cloacal apoptosis requires direct contact and signals from the WD tip and is necessary for WD-cloacal fusion. These findings may explain the mechanisms of many CAKUT.