Effect of salinity and ration size on macrophage phagocytosis in juvenile black sea bream (Mylio macrocephalus)

The effects of salinity adaptation and ration size on macrophage phagocytosis were assessed in black sea bream ( Mylio macrocephalus ) juveniles. Salinity had no effect on phagocytosis in fish that were fed a 10% ration size. Reducing ration size from 10 to 5% resulted in a significant reduction in splenic and pronephric macrophage phagocytosis of fish adapted to hyper-(33 p.p.t.) and hypo-osmotic (6 p.p.t.) salinities. The fish that were adapted to an iso-osmotic salinity (12 p.p.t.) and fed a 5% ration size were able to maintain macrophage phagocytic activity at levels comparable to those of fish that were fed a 10% ration size. It is proposed that the adaptation of sea bream to an iso-osmotic medium is beneficial in that it stimulates the immune response through activation of macrophage phagocytosis.     

Tissue Distribution, Effects of Salinity Acclimation, and Ontogeny of Aquaporin 3 in the Marine Teleost, Silver Sea Bream (Sparus sarba)

The purpose of the present study was to ascertain the tissue-specific expression of the water channel protein, aquaporin 3 (AQP3), during salinity acclimation and larval development of silver sea bream (Sparus sarba). A cDNA fragment encoding aquaporin 3 (aqp3) from silver sea bream gill was cloned and from the deduced amino acid sequence a polyclonal antibody was prepared. AQP3 was found to be present in gill, kidney, liver, brain, heart, and spleen but not in whole blood. The abundance of AQP3 was significantly highest in gills of hypoosmotic (6 ppt) and isoosmotic (12 ppt) acclimated sea bream when compared to seawater (33 ppt) and hypersaline (50 ppt)- acclimated sea bream. Spleen tissue also displayed significantly high levels of AQP3 protein in hypoosmotic and isoosmotic salinities whereas the AQP3 abundance in brain, liver, heart, and kidney remained unchanged across the range of salinities tested. The ontogenetic profile of AQP3 was also investigated from developing sea bream larvae and AQP3 was first detected at 14 days posthatch (dph) and increased steadily up to 28–46 dph. In conclusion, this study has demonstrated that AQP3 expression is modulated in gill and spleen tissue of salinity acclimated sea bream and that it can be detected relatively early during larval development.     

Lipoxygenase activity in rat kidney glomeruli, glomerular epithelial cells, and cortical tubules

We examined the possibility that renal glomerular and cortical tubular tissue has lipoxygenase activity in addition to the well established cyclo-oxygenase pathway of arachidonic acid metabolism. Homogenized rat kidney glomeruli, in the presence of meclofenamate (33 microM) and divalent cation ionophore A23187 (3 microM), metabolized octatritiated arachidonic acid to 12-hydroxyeicosatetraenoic acid and lesser amounts of 80 and/or 9-hydroxyeicosatetraenoic acid. These products were identified by thin layer chromatography, high performance liquid chromatography, and gas chromatography-mass spectroscopy. In order to rule out the synthesis of hydroxylated fatty acids by platelets and leukocytes entrapped in the glomeruli, we studied lipoxygenase products in glomerular epithelial cells after 9 days in cell culture. Homogenized glomerular epithelial cells converted octatritiated arachidonic acid to 12-hydroxyeicosatetraenoic acid solely. The lipoxygenase activity in cortical tubules was substantially less than in glomeruli and only 12-hydroxyeicosatetraenoic acid was synthesized. The production of hydroxyeicosatetraenoic acid by lipoxygenase inhibitors, nordihydroguaiaretic acid, 5,-homogenized glomeruli, glomerular epithelial cells, and cortical tubules was inhibited by three 8,11,14-eicosatetraynoic acid, and 1-phenyl-3-pyrazolidone. These data demonstrate that there is lipoxygenase activity in rat kidney glomeruli, glomerular epithelial cells and to a lesser extent cortical tubules, and may imply a role of the lipoxygenase products in the regulation of normal glomerular function and inflammatory disease of the kidney.     

Renal cortex guanylate cyclase. Preferential enrichment in glomerular membranes.

1. The localisation and some of the properties of rabbit kidney cortex guanylate cyclase (GTP pyrophosphatase lyase (cyclizing) EC 4.6.1.2) have been studied. Upon fractionation of dissociated renal cortex, guanylate cyclase activity was preferentially enriched in fractions of pure glomeruli, where its specific activity was 44.5 times that measured in tubular fragments. Most, if not all, of the glomerular activity was found to be firmly membrane-bound, whereas the guanylate cyclase activity of the tubules was mainly soluble. Therefore, particulate guanylate cyclase activity could serve as marker enzyme for kidney glomeruli. 2. All hormones or hormone-like agents tested were without effect on kidney guanylate cyclase activity. Triton X-100 stimulated both glomerular and tubular activity. 3. Considering the high cyclic GMP forming capacity of kidney glomeruli, part of the cyclic GMP found in urine might be synthetized locally in these structures.     

Role of polycystins in renal tubulogenesis

Every day, human renal tubules process 140 l of glomerular filtrate into 1 l of urine. They accomplish this by the coordinated function of distinct cell types occupying specific positions along the tubules. This precisely defined structure requires tight regulation of morphogenesis. A group of disorders termed polycystic kidney disease (PKD) is characterized by altered tubular morphology. Mutating genes involved in PKD results in renal tubules that either fail to form properly or 'forget' how to maintain their 'correct' diameter. Study of PKD proteins will elucidate the process of renal tubular morphogenesis and guide the development of therapies. Here, we focus on insights provided by study of the most common form of PKD, autosomal dominant PKD.     

Kidney morphology in sturgeons: a microdissectional and ultrastructural study

The anatomy and ultrastructure of nephrons were studied in various euryhaline and freshwater sturgeons. Microdissection failed to reveal marked differences in the nephron structure between freshwater and euryhaline fishes which might be considered as specific adaptations to the salinity of the environment. Some adaptive changes in the nephron structure were revealed by electron microscopic examination. The glomerular basal membrane is thicker in euryhaline sturgeons than in the freshwater sterlet. The processes of mesangial cells penetrating the basal membrane are much more numerous in fishes caught in the sea than in those from fresh water. Euryhaline sturgeons exhibit a great variability in the ultrastructure of epithelial cells of proximal and distal tubules. The number of mitochondria-rich cells possessing well-developed basolateral foldings is significantly higher in fishes caught in the sea. In the freshwater sterlet the ultrastructure of the epithelium of proximal and distal tubules resembles that in freshwater teleosts.
Comparison was made of the kidney morphology and ultrastructure in sturgeons, elasmo branchs and bony fishes. It is speculated that in sturgeons the adaptation to varying salinity is achieved by changes in the ultrastructure of glomeruli and differentiation of the cells of the tubular epithelium.     

Glutamic acid decarboxylase in tubules and glomeruli isolated from rat kidney cortex

4-Aminobutyric acid (GABA) synthesis was examined in purified glomeruli and tubules of rat kidney cortex that were incubated in the presence of [2,3-3H2]glutamate. The GABA that was formed was separated from glutamate using anion-exchange resin, and identified by means of an automatic amino acid analyser. In the renal cortex only the tubules were able to form GABA (35.0 nmol mg-1 h-1); the remaining GABA synthesis found in the glomerular preparations can most probably be attributed to a contamination by cortical tubules (9%), as shown by determination of a known tubular marker enzyme (L-gamma-glutamyltransferase). Hydroxylamine (1 mM) and ethanolamine-O-sulfate (10 mM), well-known inhibitors of cerebral GABA formation and GABA catabolism respectively, inhibited renal tubular GABA formation at 100% and 44% respectively.     

Renal distribution of ganglioside GM3 in rat models of types 1 and 2 diabetes

Ganglioside GM3 is particularly abundant in the kidney tissue and is thought to play an important role in the maintenance of the charge-selective filtration barrier of glomeruli. Altered expression of ganglioside GM3 was pathologically related with glomerular hypertrophy occurring in diabetic human and rat kidneys. Considering the role of GM3 ganglioside in kidney function, the aim of this study was to determine the difference in expression of GM3 ganglioside in glomeruli and tubules using immunofluorescence microscopy both in rat models of types 1 and 2 diabetes mellitus. Diabetes was induced with streptozotocin (55 mg/kg for type 1 diabetes and 35 mg/kg for type 2 diabetes) injection to male Sprague–Dawley rats which were fed with normal pellet diet (type 1 diabetes) or high-fat diet (type 2 diabetes). Rats were sacrificed 2 weeks after diabetes induction, frozen renal sections were stained with primary antibody GM3(Neu5Ac) and visualized by secondary antibody coupled with Texas red. In addition, renal gangliosides GM3 were analyzed by high-performance thin-layer chromatography followed by GM3 immunostaining. Immunofluorescent microscopy detected 1.7-fold higher GM3 expression in tubules and 1.25-fold higher GM3 in glomeruli of type 1 diabetes mellitus compared with control group. Type 2 diabetes mellitus rats showed slight GM3 increase in whole kidney, unchanged GM3 in glomeruli, but significant higher GM3 expression in tubules, compared with control animals. Taking into consideration increased tubular GM3 content in both types of diabetes, we could hypothesize the role of GM3 in early pathogenesis of diabetic nephropathy.     

Zinc deficiency during growth: influence on renal function and morphology

This study was designed to investigate the effects of moderate zinc deficiency during growth on renal morphology and function in adult life. Weaned male Wistar rats were divided into two groups and fed either a moderately zinc-deficient diet (zinc: 8 mg/kg, n=12) or a control diet (zinc: 30 mg/kg, n=12) for 60 days. We evaluated: renal parameters, NADPH-diaphorase and nitric oxide synthase activity in kidney, renal morphology and apoptotic cells in renal cortex. Zinc-deficient rats showed a decrease in glomerular filtration rate and no changes in sodium and potassium urinary excretion. Zinc deficiency decreased NADPH diaphorase activity in glomeruli and tubular segment of nephrons, and reduced activity of nitric oxide synthase in the renal medulla and cortex, showing that zinc plays an important role in preservation of the renal nitric oxide system. A reduction in nephron number, glomerular capillary area and number of glomerular nuclei in cortical and juxtamedullary areas was observed in zinc deficient kidneys. Sirius red staining and immunostaining for alpha-smooth muscle-actin and collagen III showed no signs of fibrosis in the renal cortex and medulla. An increase in the number of apoptotic cells in distal tubules and cortical collecting ducts neighboring glomeruli and, to a lesser extent, in the glomeruli was observed in zinc deficient rats. The major finding of our study is the emergence of moderate zinc deficiency during growth as a potential nutritional factor related to abnormalities in renal morphology and function that facilitates the development of cardiovascular and renal diseases in adult life.     

Altered renal morphology in transgenic mice with cholecystokinin overexpression

Although cholecystokinin is a regulatory peptide with a predominant role in the brain and the gastrointestinal tract, there is an increasing evidence for its role in the kidney. The aim of this study was to reveal morphological changes in the structure of kidney of mice with cholecystokinin overexpression by means of light, transmission and scanning electron microscope, and atomic force microscopy. Using immunohistochemistry the expression of important basement membrane proteins collagen IV, laminin and fibronectin, as well the distribution of cholecystokinin-8 in the renal structures was evaluated. The altered morphology of kidneys of mice with cholecystokinin overexpression was seen by all microscopic techniques used. The renal corpuscles were relatively small with narrow capsular lumen. The basement membranes of renal tubules were thickened and the epithelial cells were damaged, which was more pronounced for distal tubules. Characteristic feature was the increased number of vesicles seen throughout the epithelial cells of proximal and especially in distal tubules reflecting to the enhanced cellular degeneration. The relative expression of laminin but not collagen IV in the glomerular basement membrane was higher than in the tubular basement membranes. The content of fibronectin, in opposite, was higher in tubular membranes. Cholecystokinin-8 was clearly expressed in the glomeruli, in Bowman’s capsule, in proximal and distal tubules, and in collecting ducts. Ultrastructural studies showed irregularly thickened glomerular basement membranes to which elongated cytopodia of differently shaped podocytes were attached. As foot processes were often fused the number of filtration pores was decreased. In conclusion, cholecystokinin plays important role in renal structural formation and in functioning as different aspects of urine production in mice with cholecystokinin overexpression are affected-the uneven glomerular basement membrane thickening, structural changes in podocytes and in filtration slits affect glomerular filtration, while damaged tubular epithelial cells and changed composition of thickened tubular basement membranes affect reabsorption.     

Variations in renal morphology during adaptation to salinities in tilapias

Synopsis Fifteen days oldOreochromis niloticus andO. mossambicus juveniles were gradually adapted to 10, 20, 30 and 35 ppt sea water. Kidney morphology was observed after transfer to higher salinities and compared with freshwater controls. Despite differences in salinity tolerance, both species have similar transformations when transferred at high salinity, particularly reduction of the glomerular area after 2 months adaptation to sea water, and change in tubule morphology.     

Glomeruli and renal tubules are restricted to the cranial kidney of the adult estuarine Sphoeroides testudineus

The kidney of the pufferfish Sphoeroides testudineus , an abundant tropical euryhaline estuarine species of the western Atlantic Ocean found in southern Brazil (in salinities ranging from 0 to 34) has a large and laterally spread cranial red portion, and a very thin and pale caudal portion. When studied under light and transmission electron microscopy, the cranial kidney displayed glomeruli and renal tubules surrounded by haematopoietic tissue. These tubules appeared to drain into a single large convoluted collecting duct with a wide lumen and thick pseudostratified epithelium, the mesonephric duct, which constituted the sole structure of the caudal kidney. Apical microvillae were viewed in the renal tubules, as well as in the mesonephric duct. Basal mitochondria and membrane infoldings were observed in the renal tubules. Abundant more basally‐located mitochondria and electron‐dense vesicles, mainly in the apical cytoplasm, were observed along the entire length of the mesonephric duct. Aposomes (blebs) were frequently observed in the mesonephric duct, both by light‐ and electron‐microscopy. This euryhaline estuarine pufferfish has thus been revealed to possess a rare type of kidney.     

Diabetic nephropathy induces alterations in the glomerular and tubule lipid profiles

Diabetic nephropathy (DN) is a major life-threatening complication of diabetes. Renal lesions affect glomeruli and tubules, but the pathogenesis is not completely understood. Phospholipids and glycolipids are molecules that carry out multiple cell functions in health and disease, and their role in DN pathogenesis is unknown. We employed high spatial resolution MALDI imaging MS to determine lipid changes in kidneys of eNOS^−/− db/db mice, a robust model of DN. Phospholipid and glycolipid structures, localization patterns, and relative tissue levels were determined in individual renal glomeruli and tubules without disturbing tissue morphology. A significant increase in the levels of specific glomerular and tubular lipid species from four different classes, i.e., gangliosides, sulfoglycosphingolipids, lysophospholipids, and phosphatidylethanolamines, was detected in diabetic kidneys compared with nondiabetic controls. Inhibition of nonenzymatic oxidative and glycoxidative pathways attenuated the increase in lipid levels and ameliorated renal pathology, even though blood glucose levels remained unchanged. Our data demonstrate that the levels of specific phospho- and glycolipids in glomeruli and/or tubules are associated with diabetic renal pathology. We suggest that hyperglycemia-induced DN pathogenic mechanisms require intermediate oxidative steps that involve specific phospholipid and glycolipid species.     

The importance of the olfactory rosettes in maintaining pituitary prolactin and prolactin-releasing peptide levels during hyposmotic acclimation in silver sea bream (Sparus sarba)

A potential role of the olfactory rosettes in maintaining prolactin (PRL) and prolactin-releasing peptide (PrRP) levels was examined in the euryhaline silver sea bream (Sparus sarba). The olfactory rosettes were surgically removed in silver sea bream adapted to hypo- (6 ppt) and hyper-osmotic (33 ppt) salinities and the mRNA expression of the two previously identified freshwater-adapting factors, prolactin (PRL) and prolactin-releasing peptide (PrRP), in silver sea bream was measured. The elevation of pituitary PRL and PrRP mRNA expression levels as seen in 6 ppt-adapted fish was abolished by surgical removal of the olfactory rosettes. The PRL and PrRP expression levels in fish adapted to 6 ppt were significantly lowered following olfactory rosette removal. On the other hand, hypothalamic PrRP mRNA expression in 6 ppt-adapted fish did not change. Specific signals for Na(+)-K(+)-ATPase but not CFTR mRNA expression were detected in the surface layers of olfactory epithelial cells by in situ hybridization. The mRNA abundance of CFTR and Na(+)-K(+)-ATPase α and β subunits remained unchanged in the olfactory rosette of silver sea bream adapted to 0, 6, 12, 33 and 50 ppt for 4 weeks and in fish abruptly transferred from 33 ppt to 6 ppt. Data obtained from the olfactory rosette removal experiments suggest a possible role of the olfactory system for maintaining PRL and PrRP expression during hyposmotic acclimation in sea bream.     

Modification of genital kidney nephrons for sperm transport in a plethodontid salamander,Eurycea longicauda

Salamanders possess kidneys with two distinct regions: a caudal pelvic portion and cranial genital portion. Nephrons of the pelvic region are responsible for urine formation and transport. Nephrons of the genital region transport sperm from testes to Wolffian ducts; however, nephrons of the genital region possess all the same functional regions found in pelvic kidney nephrons that are involved with urine formation and transport (renal corpuscles, proximal tubules, distal tubules, and collecting ducts). Morphological similarities between pelvic and genital regions stimulated past researchers to hypothesize that nephrons of genital kidneys possess dual function; that is, sperm transport and urine formation/transport. Considering size of glomeruli is directly related to the total amount of blood plasma filtered into the Bowman's space, we tested the hypothesis that nephrons of genital kidneys have reduced urine formation function by comparing glomerular size between nephrons of pelvic and genital kidney regions in Eurycea longicauda with general histological techniques. Light microscopy analysis revealed that glomeruli of pelvic kidneys were significantly larger than those measured from genital kidneys. Transmission electron microscopy analysis also revealed modifications in genital kidney nephrons when compared to pelvic kidney nephrons that suggested a decrease in urine formation function in genital kidneys. Such modifications included a decrease in basal and lateral plasma membrane folding in genital kidney proximal and distal tubules compared to that of pelvic kidney proximal and distal tubules. Genital kidney proximal tubules were also ciliated, which was not observed in pelvic kidney proximal tubules. In conclusion, although structurally similar at the histological level, it appears that nephrons of genital kidneys have decreased urine formation function based on glomerular size comparison and nephron ultrastructure.     

Light and Electron Microscopical Studies of the Renal Lesion in Dogs With Pyometra

Kidney biopsies from 23 bitches with pyometra and an entire kidney from four pyometra bitches were examined by light microscopy. Kidney tissue was also taken from three bitches at different intervals after ovariohysterectomy for pyometra. All the pyometra bitches had membranous glomerulonephritis or mixed proliferative and membranous glomerulonephritis. Two of the bitches had intraglomerular hyaline nodules resembling those seen in conjunction with diabetes in human beings. The degree of glomerular damage could be correlated with the reduction in glomerular filtration rate determined by function tests. The proximal tubules generally contained numerous hyaline droplets but the degree of this change could not be correlated to the degree of glomerular damage. A yellow pigment, a lipofuscin, was regularly present in the proximal tubules as well as epithelial proliferation and mitoses. Focal atrophy of tubules also occurred, presumably because of obliteration of glomeruli. The cortical interstitium contained collections of mature and immature plasma cells, often surrounding the glomeruli. When the kidneys from three bitches were examined after ovariohysterectomy for pyometra, the glomerular damage in two had regressed to leave only slight thickening of the capillary walls. In the third bitch, examined only 14 days after ovariohysterectomy, healing was partial. Kidney tissue from five bitches was also examined by electron microscopy. The glomerular endothelial cells were swollen and the basement membrane was grealy thickened. With more severe degrees of glomerular damage, an electron-dense material was deposited along the inner surface of the basement membrane and the swollen mesangial cells contained numerous inclusions. There was focal fusion of the foot processes of the glomerular epithelial cells; in one bitch with heavy proteinuria, the fusion was widespread. The proximal tubules contained numerous protein absorption droplets representing resorbed protein. The tubular basement membrane at all levels was thickened. Because of similarities with some other types of renal damage (nephrotoxic nephritis in dogs and acute proliferative glomerulonephritis in human beings), the possibility is broached that the renal lesion in pyometra is the result of an immunobiological process.     

Metabolic and osmoregulatory changes in response to reduced salinities in the red grouper, Epinephelus akaara (Temminck & Schlegel), and the black sea bream, Mylio macrocephalus (Basilewsky)

Red groupers (Epinephelus akaara Temminck & Schlegel) and black sea breams (Mylio macrocephalus Basilewsky) were transferred from 30‰ into 3, 7, 12, 20, and 30‰ salinity. Fish were sampled at 0, 6, 24, 96, 168 and 336h after transfer. Serum osmolality, glucose, protein, Na⁺, K⁺, Ca²⁺, liver glycogen, liver protein, muscle water and haematocrit were determined. In general, transient disturbances in these variables were observed after transfer. For both species, no tissue hydration was observed upon acclimation to different salinities, whereas a progressive increase in haematocrit value was found as salinity decreased. Liver glycogen of both species, however, was higher in hypo-osmotic salinities. Serum Na⁺ of the red groupers declined upon acclimation to 7‰ salinity but the opposite was found for the black sea breams. The results indicate that both species are extremely euryhaline, and physiological stress is unlikely to occur within the salinity regime of 7 to 30‰ Comparatively, the black sea bream appears to be a more efficient osmoregulator.     

Claudin-6 localized in tight junctions of rat podocytes

Tight junctions rarely exist in podocytes of the normal renal glomerulus, whereas they are the main intercellular junctions of podocytes in nephrosis and in the early stage of development. Claudins have been identified as tight junction-specific integral membrane proteins. Those of podocytes, however, remain to be elucidated. In the present study, we investigated the expression and localization of claudin-6 in the rat kidney, especially in podocytes. Western blot analysis and RT-PCR revealed that the neonatal kidney expressed much higher levels of claudin-6 than the adult kidney. Immunofluorescence microscopy showed intense claudin-6 staining in most of the tubules and glomeruli in neonates. The staining in tubules declined distinctly in adults, whereas staining in glomeruli was well preserved during development. Claudin-6 in glomeruli was distributed along the glomerular capillary wall and colocalized with zonula occludens-1. The staining became conspicuous after kidney perfusion with protamine sulfate (PS) to increase tight junctions in podocytes. Immunoelectron microscopy showed that immunogold particles for claudin-6 were accumulated at close cell-cell contact sites of podocytes in PS-perfused kidneys, whereas a very limited number of immunogold particles were detected, mainly on the basal cell membrane and occasionally at the slit diaphragm and close cell-cell contact sites in normal control kidneys. In puromycin aminonucleoside nephrosis, immunogold particles were also found mainly at cell-contact sites of podocytes. These findings indicate that claudin-6 is a transmembrane protein of tight junctions in podocytes during development and under pathological conditions.     

APOBEC3G expression is restricted to epithelial cells of the proximal convoluted tubules and is not expressed in the glomeruli of macaques.

The Vif protein of human immunodeficiency virus-1 (HIV-1) interacts with members of the APOBEC family of cytidine deaminases. In this study, we isolated RNA from renal cortex as well as from isolated glomeruli and tubulointerstitial fractions from two pigtailed macaques that were exsanguinated and perfused with saline. RT-PCR results indicate that APOBEC3G was detected in the tubule fractions but not in the glomerular fractions. Immunoblot analysis using lysates prepared from these same fractions and a monoclonal antibody to APOBEC3G confirmed the RT-PCR findings. To determine which cell types express APOBEC3G, immunohistochemical studies were performed using this monoclonal antibody on renal cortical sections. Our results clearly show that the glomeruli do not express APOBEC3G but that select tubules within the cortex express APOBEC3G at high levels. To further differentiate the distribution of APOBEC3G expression, serial sections were stained with the lectins Dolichos biflorus agglutinin (DBA) and Phaseolus vulgaris erythroagglutinin (PHA-E), which differentially bind to epithelial cells of the tubules and glomeruli. Our results indicate that APOBEC3G expression was restricted to PHA-E-staining tubules and not DBA-staining tubules, suggesting that APOBEC3G expression was restricted to proximal convoluted tubules. These findings suggest that infection of epithelial cells of proximal renal tubules could suppress Vif-defective HIV-1 replication, whereas infection of cells of the glomeruli, a major target of HIV-associated nephropathy, could act as a reservoir for the replication of Vif-defective HIV-1.     

p120 catenin is required for normal renal tubulogenesis and glomerulogenesis

Defects in the development or maintenance of tubule diameter correlate with polycystic kidney disease. Here, we report that absence of the cadherin regulator p120 catenin (p120ctn) from the renal mesenchyme prior to tubule formation leads to decreased cadherin levels with abnormal morphologies of early tubule structures and developing glomeruli. In addition, mutant mice develop cystic kidney disease, with markedly increased tubule diameter and cellular proliferation, and detached luminal cells only in proximal tubules. The p120ctn homolog Arvcf is specifically absent from embryonic proximal tubules, consistent with the specificity of the proximal tubular phenotype. p120ctn knockdown in renal epithelial cells in 3D culture results in a similar cystic phenotype with reduced levels of E-cadherin and active RhoA. We find that E-cadherin knockdown, but not RhoA inhibition, phenocopies p120ctn knockdown. Taken together, our data show that p120ctn is required for early tubule and glomerular morphogenesis, as well as control of luminal diameter, probably through regulation of cadherins.