Extracellular vesicles from human bone marrow mesenchymal stem cells repair organ damage caused by cadmium poisoning in a medaka model.

Treatment modalities for kidney disease caused by long-term exposure to heavy metals, such as cadmium (Cd), are limited. Often, chronic, long-term environmental exposure to heavy metal is not recognized in the early stages; therefore, chelation therapy is not an effective option. Extracellular vesicles (EVs) derived from stem cells have been demonstrated to reduce disease pathology in both acute and chronic kidney disease models.

Wtip is required for proepicardial organ specification and cardiac left/right asymmetry in zebrafish.

Wilm's tumor 1 interacting protein (Wtip) was identified as an interacting partner of Wilm's tumor protein (WT1) in a yeast two-hybrid screen. WT1 is expressed in the proepicardial organ (PE) of the heart, and mouse and zebrafish wt1 knockout models appear to lack the PE. Wtip's role in the heart remains unexplored.

A developmentally plastic adult mouse kidney cell line spontaneously generates multiple adult kidney structures.

Despite exciting new possibilities for regenerative therapy posed by the ability to induce pluripotent stem cells, recapitulation of three-dimensional kidneys for repair or replacement has not been possible. ARID3a-deficient mouse tissues generated multipotent, developmentally plastic cells. Therefore, we assessed the adult mouse ARID3a-/- kidney cell line, KKPS5, which expresses renal progenitor surface markers as an alternative cell source for modeling kidney development.

Workshop report: The medaka model for comparative assessment of human disease mechanisms.

Results of recent studies showing the utility of medaka as a model of various human disease states were presented at the 7th Aquatic Models of Human Disease Conference (December 13-18, 2014, Austin, TX). This conference brought together many of the most highly regarded national and international scientists that employ the medaka model in their investigations. To take advantage of this opportunity, a cohort of established medaka researchers were asked to stay an extra day and represent the medaka scientific community in a workshop entitled "The Medaka Model for Comparative Assessment of Human Disease Mechanisms.

Nephrin and Podocin functions are highly conserved between the zebrafish pronephros and mammalian metanephros.

The slit diaphragm (SD) is a highly specialized intercellular junction between podocyte foot processes and is crucial in the formation of the filtration barrier in the renal glomeruli. Zebrafish Nephrin and Podocin are important in the formation of the podocyte SD and mutations in NEPHRIN and PODOCIN genes cause human nephrotic syndrome. In the present study, the zebrafish Podocin protein was observed to be predominantly localized in the pronephric glomerular podocytes, as previously reported for Nephrin.

Podocalyxin regulates pronephric glomerular development in zebrafish.

Vertebrate glomerular podocytes possess a highly sialylated transmembrane glycoprotein, Podocalyxin. In mammals, the sialic acid of Podocalyxin plays a crucial role in the formation of the characteristic podocyte architecture required for glomerular filtration. We examined the function of Podocalyxin in the developing zebrafish pronephros by disrupting the expression of through the use of morpholino antisense oligonucleotides.

Medaka fish, Oryzias latipes, as a model for human obesity-related glomerulopathy.

Obesity, an ongoing significant public health problem, is a part of complex disease characterized as metabolic syndrome. Medaka and zebrafish are useful aquatic experimental animals widely used in the field of toxicology and environmental health sciences and as a human disease models. In medaka, simple feeding of a high fat diet (HFD) can induce body weight gain, excessive accumulation of visceral adipose tissue, hyperglycemia, hyperlipidemia, and steatohepatitis, which mimics human metabolic syndrome.

Developmental localization of nephrin in zebrafish and medaka pronephric glomerulus.

Slit diaphragm (SD) is a highly specialized intercellular junction between podocyte foot processes and plays a crucial role in the formation of the filtration barrier. In this study, we examined the developmental localization of Nephrin, an essential component of SD, in the pronephric glomerulus of zebrafish and medaka. In the mature glomerulus of both fish, Nephrin is localized along the glomerular basement membrane as seen in mammals, indicating that Nephrin is localized at the SD.

Wtip and Vangl2 are required for mitotic spindle orientation and cloaca morphogenesis.

Defects in cilia and basal bodies function are linked to ciliopathies, which result in kidney cyst formation. Recently, cell division defects have been observed in cystic kidneys, but the underlying mechanisms of such defects remain unclear. Wtip is an LIM domain protein of the Ajuba/Zyxin family, but its role in ciliogenesis during embryonic development has not been previously described.

A comparative analysis of glomerulus development in the pronephros of medaka and zebrafish.

The glomerulus of the vertebrate kidney links the vasculature to the excretory system and produces the primary urine. It is a component of every single nephron in the complex mammalian metanephros and also in the primitive pronephros of fish and amphibian larvae. This systematic work highlights the benefits of using teleost models to understand the pronephric glomerulus development.

Structural disorganization of pronephric glomerulus in zebrafish mpp5a/nagie oko mutant.

Background: The podocyte slit diaphragm (SD) is an essential component of the selective filtration barrier in the glomerulus. Several structural proteins required for formation and maintenance of SD have been identified; however, molecular mechanisms regulating these proteins are still limited.

Results: Here, we demonstrate that MAGUK p55 subfamily member 5a (Mpp5a)/Nagie oko, a component of the Crb multi-protein complex, was colocalized with an SD-associated protein ZO-1 in the zebrafish pronephric glomerulus.

Adaptation process for standing postural control in individuals with hemiparesis.

Purpose: To study the adaptation process for standing postural control in patients with hemiparesis after stroke.

Methods: The changes of a standing posture developed in nine hemiparetic patients who had never maintained an upright stance alone (aged 48-62 years; 6-19 days after stroke) was evaluated by recording ground reaction forces and surface electromyographic (EMG) from lower limbs. A 60-s standing trial without any instruction about body alignment was repeated five times, and the experience-related changes of centre of pressure (COP) and integrated EMG data were estimated.

Nde1-mediated inhibition of ciliogenesis affects cell cycle re-entry.

The primary cilium is an antenna-like organelle that is dynamically regulated during the cell cycle. Ciliogenesis is initiated as cells enter quiescence, whereas resorption of the cilium precedes mitosis. The mechanisms coordinating ciliogenesis with the cell cycle are unknown.

A polycystin-2 (TRPP2) dimerization domain essential for the function of heteromeric polycystin complexes.

Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in two genes, PKD1 and PKD2, which encode polycystin-1 (PC1) and polycystin-2 (PC2), respectively. Earlier work has shown that PC1 and PC2 assemble into a polycystin complex implicated in kidney morphogenesis. PC2 also assembles into homomers of uncertain functional significance.

Identification and functional characterization of an N-terminal oligomerization domain for polycystin-2.

Autosomal dominant polycystic kidney disease (ADPKD), the most common inherited cause of kidney failure, is caused by mutations in either PKD1 (85%) or PKD2 (15%). The PKD2 protein, polycystin-2 (PC2 or TRPP2), is a member of the transient receptor potential (TRP) superfamily and functions as a non-selective calcium channel. PC2 has been found to form oligomers in native tissues suggesting that it may form functional homo- or heterotetramers with other subunits, similar to other TRP channels.

Fish and frogs: models for vertebrate cilia signaling.

The presence of cilia in many vertebrate cell types and its function has been ignored for many years. Only in the past few years has its importance been rediscovered. In part, this was triggered by the realization that many gene products mutated in polycystic kidney diseases are localized to cilia and dysfunctional cilia result in kidney disease.

The zebrafish fleer gene encodes an essential regulator of cilia tubulin polyglutamylation.

Cilia and basal bodies are essential organelles for a broad spectrum of functions, including the development of left-right asymmetry, kidney function, cerebrospinal fluid transport, generation of photoreceptor outer segments, and hedgehog signaling. Zebrafish fleer (flr) mutants exhibit kidney cysts, randomized left-right asymmetry, hydrocephalus, and rod outer segment defects, suggesting a pleiotropic defect in ciliogenesis. Positional cloning flr identified a tetratricopeptide repeat protein homologous to the Caenorhabditis elegans protein DYF1 that was highly expressed in ciliated cells.

Polycystin-2 immunolocalization and function in zebrafish.

Polycystin-2 functions as a cation-permeable transient receptor potential ion channel in kidney epithelial cells and when mutated results in human autosomal dominant polycystic kidney disease. For further exploration of the in vivo functions of Polycystin-2, this study examined its expression and function during zebrafish embryogenesis. pkd2 mRNA is ubiquitously expressed, and its presence in the larval kidney could be confirmed by reverse transcription-PCR on isolated pronephroi.

Identification of an N-terminal glycogen synthase kinase 3 phosphorylation site which regulates the functional localization of polycystin-2 in vivo and in vitro.

PKD2 is mutated in 15% of patients with autosomal dominant polycystic kidney disease. Polycystin-2 (PC2), the PKD2 protein, is a non-selective Ca(2+)-permeable cation channel which may function at the cell surface and ER. Nevertheless, the factors that regulate the dynamic translocation of PC2 between the ER and other compartments are not well understood.

Polycystin-1, STAT6, and P100 function in a pathway that transduces ciliary mechanosensation and is activated in polycystic kidney disease.

Primary cilia are implicated in the pathogenesis of autosomal-dominant polycystic kidney disease (ADPKD), which results from defects in polycystin-1 (PC1), but the function of PC1 remains poorly understood. Here, we show that PC1 undergoes proteolytic cleavage that results in nuclear translocation of its cytoplasmic tail. The PC1 tail interacts with the transcription factor STAT6 and the coactivator P100, and it stimulates STAT6-dependent gene expression.

Inversin, the gene product mutated in nephronophthisis type II, functions as a molecular switch between Wnt signaling pathways.

Cystic renal diseases are caused by mutations of proteins that share a unique subcellular localization: the primary cilium of tubular epithelial cells. Mutations of the ciliary protein inversin cause nephronophthisis type II, an autosomal recessive cystic kidney disease characterized by extensive renal cysts, situs inversus and renal failure. Here we report that inversin acts as a molecular switch between different Wnt signaling cascades.

roundabout4 is essential for angiogenesis in vivo.

Stereotypical patterns of vascular and neuronal networks suggest that specific genetic programs tightly control path determination and, consequently, angiogenesis and axon-guidance mechanisms. Our study focuses on one member of the roundabout family of receptors, which traditionally mediate repulsion from the midline. Here, we characterize a fourth member of this family, roundabout4 (robo4), which is the predominant roundabout (robo) that is expressed in embryonic zebrafish vasculature.

Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination.

Nephronophthisis (NPHP), an autosomal recessive cystic kidney disease, leads to chronic renal failure in children. The genes mutated in NPHP1 and NPHP4 have been identified, and a gene locus associated with infantile nephronophthisis (NPHP2) was mapped. The kidney phenotype of NPHP2 combines clinical features of NPHP and polycystic kidney disease (PKD).

A defect in a novel Nek-family kinase causes cystic kidney disease in the mouse and in zebrafish.

The murine autosomal recessive juvenile cystic kidney (jck) mutation results in polycystic kidney disease. We have identified in jck mice a mutation in Nek8, a novel and highly conserved member of the Nek kinase family. In vitro expression of mutated Nek8 results in enlarged, multinucleated cells with an abnormal actin cytoskeleton.