-
Proceedings of the National Academy of... Dec 2005Mutation of the gene encoding the Mediator component thyroid hormone receptor-associated protein (TRAP)230/MED12 affects the development of multiple systems in zebrafish...
Mutation of the gene encoding the Mediator component thyroid hormone receptor-associated protein (TRAP)230/MED12 affects the development of multiple systems in zebrafish embryogenesis. We isolated two ethylnitrosourea-induced alleles in the gene encoding this protein and named the locus kohtalo (kto) after the homologous locus in Drosophila. Homozygous kto mutant zebrafish embryos show defects in brain, neural crest, and kidney development and die at approximately 6 days postfertilization. In the affected tissues, differentiation is initiated and many cell type-specific genes are expressed, but there is a failure of morphogenesis and failure to complete differentiation. These results suggest that critical targets of TRAP230 function may include proteins important for cell mobility, cell sorting, and tissue assembly.
Topics: Animals; Base Sequence; Brain; Cloning, Molecular; Drosophila Proteins; Embryo, Nonmammalian; Eye Proteins; Gene Expression Regulation, Developmental; Kidney; Mediator Complex; Molecular Sequence Data; Mutation; Neural Crest; Phenotype; Transcription Factors; Zebrafish; Zebrafish Proteins
PubMed: 16344459
DOI: 10.1073/pnas.0509457102 -
Current Pediatric Reviews 2014Renal development begins in-utero and continues throughout childhood. Almost one-third of all developmental anomalies include structural or functional abnormalities of... (Review)
Review
Renal development begins in-utero and continues throughout childhood. Almost one-third of all developmental anomalies include structural or functional abnormalities of the urinary tract. There are three main phases of in-utero renal development: Pronephros, Mesonephros and Metanephros. Within three weeks of gestation, paired pronephri appear. A series of tubules called nephrotomes fuse with the pronephric duct. The pronephros elongates and induces the nearby mesoderm, forming the mesonephric (Woffian) duct. The metanephros is the precursor of the mature kidney that originates from the ureteric bud and the metanephric mesoderm (blastema) by 5 weeks of gestation. The interaction between these two components is a reciprocal process, resulting in the formation of a mature kidney. The ureteric bud forms the major and minor calyces, and the collecting tubules while the metanephrogenic blastema develops into the renal tubules and glomeruli. In humans, all of the nephrons are formed by 32 to 36 weeks of gestation. Simultaneously, the lower urinary tract develops from the vesico urethral canal, ureteric bud and mesonephric duct. In utero, ureters deliver urine from the kidney to the bladder, thereby creating amniotic fluid. Transcription factors, extracellular matrix glycoproteins, signaling molecules and receptors are the key players in normal renal development. Many medications (e.g., aminoglycosides, cyclooxygenase inhibitors, substances that affect the renin-angiotensin aldosterone system) also impact renal development by altering the expression of growth factors, matrix regulators or receptors. Thus, tight regulation and coordinated processes are crucial for normal renal development.
Topics: Cell Differentiation; Extracellular Matrix; Gene Expression Regulation, Developmental; Humans; Kidney Tubules, Collecting; Mesonephros; Pronephros; Renin-Angiotensin System; Signal Transduction; Urinary Tract; Urogenital System
PubMed: 25088264
DOI: 10.2174/157339631002140513101950 -
Frontiers in Genetics 2022The (Solute carrier family 12 member 3) gene encodes a sodium-chloride cotransporter and mediates Na and Cl reabsorption in the distal convoluted tubule of kidneys. An... (Review)
Review
The (Solute carrier family 12 member 3) gene encodes a sodium-chloride cotransporter and mediates Na and Cl reabsorption in the distal convoluted tubule of kidneys. An experimental study has previously showed that with knockdown of zebrafish ortholog, slc12a3 led to structural abnormality of kidney pronephric distal duct at 1-cell stage, suggesting that may have genetic effects in renal disorders. Many clinical reports have demonstrated that the function-loss mutations in the gene, mainly including Thr60Met, Asp486Asn, Gly741Arg, Leu859Pro, Arg861Cys, Arg913Gln, Arg928Cys and Cys994Tyr, play the pathogenic effects in Gitelman syndrome. This kidney disease is inherited as an autosomal recessive trait. In addition, several population genetic association studies have indicated that the single nucleotide variant Arg913Gln in the gene is associated with diabetic kidney disease in type 2 diabetes subjects. In this review, we first summarized bioinformatics of the gene and its genetic variation. We then described the different genetic and biological effects of in Gitelman syndrome and diabetic kidney disease. We also discussed about further genetic and biological analyses of as pharmacokinetic targets of diuretics.
PubMed: 35591852
DOI: 10.3389/fgene.2022.799224 -
Development (Cambridge, England) Dec 1999We report a study on the specification of the glomus, the filtration device of the amphibian pronephric kidney, using an explant culturing strategy in Xenopus laevis....
We report a study on the specification of the glomus, the filtration device of the amphibian pronephric kidney, using an explant culturing strategy in Xenopus laevis. Explants of presumptive pronephric mesoderm were dissected from embryos of mid-gastrula to swimming tadpole stages. These explants were cultured within ectodermal wraps and analysed by RT-PCR for the presence of the Wilm's Tumour-1 gene, xWT1, a marker specific for the glomus at the stages analysed, together with other mesodermal markers. We show that the glomus is specified at stage 12.5, the same stage at which pronephric tubules are specified. We have previously shown that pronephric duct is specified somewhat later, at stage 14. Furthermore, we have analysed the growth factor inducibility of the glomus in the presence or absence of retinoic acid (RA) by RT-PCR. We define for the first time the conditions under which these growth factors induce glomus tissue in animal cap tissue. Activin together with high concentrations of RA can induce glomus tissue from animal cap ectoderm. Unlike the pronephric tubules, the glomus can also be induced by FGF and RA.
Topics: Activins; Animals; Embryonic Induction; Fibroblast Growth Factors; Gastrula; Inhibins; Kidney; Tretinoin; Xenopus laevis
PubMed: 10572058
DOI: 10.1242/dev.126.24.5847 -
Development (Cambridge, England) May 2000Pax genes are important developmental regulators and function at multiple stages of vertebrate kidney organogenesis. In this report, we have used the zebrafish pax2.1...
Pax genes are important developmental regulators and function at multiple stages of vertebrate kidney organogenesis. In this report, we have used the zebrafish pax2.1 mutant no isthmus to investigate the role for pax2.1 in development of the pronephros. We demonstrate a requirement for pax2.1 in multiple aspects of pronephric development including tubule and duct epithelial differentiation and cloaca morphogenesis. Morphological analysis demonstrates that noi(- )larvae specifically lack pronephric tubules while glomerular cell differentiation is unaffected. In addition, pax2.1 expression in the lateral cells of the pronephric primordium is required to restrict the domains of Wilms' tumor suppressor (wt1) and vascular endothelial growth factor (VEGF) gene expression to medial podocyte progenitors. Ectopic podocyte-specific marker expression in pronephric duct cells correlates with loss of expression of the pronephric tubule and duct-specific markers mAb 3G8 and a Na(+)/K(+) ATPase (&agr;)1 subunit. The results suggest that the failure in pronephric tubule differentiation in noi arises from a patterning defect during differentiation of the pronephric primordium and that mutually inhibitory regulatory interactions play an important role in defining the boundary between glomerular and tubule progenitors in the forming nephron.
Topics: Animals; Body Patterning; DNA-Binding Proteins; Kidney Glomerulus; Kidney Tubules; Mutagenesis; PAX2 Transcription Factor; Transcription Factors; Zebrafish; Zebrafish Proteins
PubMed: 10769233
DOI: 10.1242/dev.127.10.2089 -
Kidney International May 2008Nephrons possess a segmental organization where each segment is specialized for the secretion and reabsorption of particular solutes. The developmental control of... (Review)
Review
Nephrons possess a segmental organization where each segment is specialized for the secretion and reabsorption of particular solutes. The developmental control of nephron segment patterning remains one of the enigmas within the field of renal biology. Achieving an understanding of the mechanisms that direct nephron segmentation has the potential to shed light on the causes of kidney birth defects and renal diseases in humans. Researchers studying embryonic kidney development in zebrafish and Xenopus have recently demonstrated that the pronephric nephrons in these vertebrates are segmented in a similar fashion as their mammalian counterparts. Further, it has been shown that retinoic acid signaling establishes proximodistal segment identities in the zebrafish pronephros by modulating the expression of renal transcription factors and components of signaling pathways that are known to direct segment fates during mammalian nephrogenesis. These findings present the zebrafish model as an excellent genetic system in which to interrogate the conserved developmental pathways that control nephron segmentation in both lower vertebrates and mammals.
Topics: Animals; Models, Animal; Nephrons; Organogenesis; Tretinoin; Zebrafish
PubMed: 18322540
DOI: 10.1038/ki.2008.37 -
The American Journal of Anatomy Aug 1989The pronephric kidneys were examined in upstream migrant sea lampreys, Petromyzon marinus L., by transmission and scanning electron microscopy. Each pronephros consists...
The pronephric kidneys were examined in upstream migrant sea lampreys, Petromyzon marinus L., by transmission and scanning electron microscopy. Each pronephros consists of an enlarged renal corpuscle (glomus) and ciliated nephrostomes, but there are no renal tubules. The renal corpuscle contains an extensive mesangium, which consists of a highly fibrous extracellular matrix, numerous mesangial cells, granulocytes, and macrophages. The extracellular matrix contains microfibrils with a morphology similar to amyloid P microfibrils, fibrils with a periodicity similar to fibrin, and abundant collagen. Often these fibrillar components are aggregated in the region of the basement membrane, giving it a thickened appearance. Some podocytes of the visceral epithelium appear swollen, and their cytoplasm contains numerous vacuolar inclusions, and many have only primary major processes with only a few or no foot processes. The morphological features of the pronephric kidney of the lamprey at this time in the life cycle reflect the regression of this organ, but some features also resemble those seen in renal pathologies of higher vertebrates.
Topics: Animals; Fishes; Glomerular Mesangium; Kidney; Lampreys; Microscopy, Electron; Microscopy, Electron, Scanning; Nephrons
PubMed: 2782283
DOI: 10.1002/aja.1001850406 -
Development, Growth & Differentiation Apr 1993Correlation between activin and retinoic acid (RA), both of which affect early amphibian development, was studied using Xenopus laevis embryos. In the first set of...
Correlation between activin and retinoic acid (RA), both of which affect early amphibian development, was studied using Xenopus laevis embryos. In the first set of experiments, two isomers of RA, all-trans RA and 13-cis RA, were compared in terms of stability of biological activity against light. Xenopus blastulae were dipped in RA solutions which had either been kept away from light, or had been exposed to light for a few hours. At doses ranging from 10 to 10 M, RA elicited head deformity. All-trans RA, under both dark and light conditions, had similarly potent effects. On the other hand, 13-cis RA under dark conditions had much weaker effects than it did under light conditions. In the second set of experiments, activin was mixed with all-trans RA, and the inducing effects on the animal cap explants were investigated. Activin at a concentration of 10 ng/ml induced notochord. In combination with 10 M RA, muscle was well induced instead of notochord. In combination with 10 M RA, pronephric tubules were markedly induced. Pronephric tubules were never induced by activin alone, at any of the various concentrations employed. This is the first report on the very high frequency of induction of pronephric tubules by the combination of activin A and all-trans RA in the Xenopus ectoderm.
PubMed: 37281298
DOI: 10.1111/j.1440-169X.1993.00123.x -
PLoS Genetics Apr 2015Lowe syndrome and Dent-2 disease are caused by mutation of the inositol 5-phosphatase OCRL1. Despite our increased understanding of the cellular functions of OCRL1, the...
Lowe syndrome and Dent-2 disease are caused by mutation of the inositol 5-phosphatase OCRL1. Despite our increased understanding of the cellular functions of OCRL1, the underlying basis for the renal tubulopathy seen in both human disorders, of which a hallmark is low molecular weight proteinuria, is currently unknown. Here, we show that deficiency in OCRL1 causes a defect in endocytosis in the zebrafish pronephric tubule, a model for the mammalian renal tubule. This coincides with a reduction in levels of the scavenger receptor megalin and its accumulation in endocytic compartments, consistent with reduced recycling within the endocytic pathway. We also observe reduced numbers of early endocytic compartments and enlarged vacuolar endosomes in the sub-apical region of pronephric cells. Cell polarity within the pronephric tubule is unaffected in mutant embryos. The OCRL1-deficient embryos exhibit a mild ciliogenesis defect, but this cannot account for the observed impairment of endocytosis. Catalytic activity of OCRL1 is required for renal tubular endocytosis and the endocytic defect can be rescued by suppression of PIP5K. These results indicate for the first time that OCRL1 is required for endocytic trafficking in vivo, and strongly support the hypothesis that endocytic defects are responsible for the renal tubulopathy in Lowe syndrome and Dent-2 disease. Moreover, our results reveal PIP5K as a potential therapeutic target for Lowe syndrome and Dent-2 disease.
Topics: Animals; Cell Polarity; Endocytosis; Endosomes; Gene Deletion; Low Density Lipoprotein Receptor-Related Protein-2; Oculocerebrorenal Syndrome; Phosphoric Monoester Hydrolases; Phosphotransferases (Alcohol Group Acceptor); Pronephros; Zebrafish; Zebrafish Proteins
PubMed: 25838181
DOI: 10.1371/journal.pgen.1005058 -
Developmental Biology Oct 2014The kidney is a homeostatic organ required for waste excretion and reabsorption of water, salts and other macromolecules. To this end, a complex series of developmental...
The kidney is a homeostatic organ required for waste excretion and reabsorption of water, salts and other macromolecules. To this end, a complex series of developmental steps ensures the formation of a correctly patterned and properly proportioned organ. While previous studies have mainly focused on the individual signaling pathways, the formation of higher order receptor complexes in lipid rafts is an equally important aspect. These membrane platforms are characterized by differences in local lipid and protein compositions. Indeed, the cells in the Xenopus pronephric kidney were positive for the lipid raft markers ganglioside GM1 and Caveolin-1. To specifically interfere with lipid raft function in vivo, we focused on the Sterol Carrier Protein 2 (scp2), a multifunctional protein that is an important player in remodeling lipid raft composition. In Xenopus, scp2 mRNA was strongly expressed in differentiated epithelial structures of the pronephric kidney. Knockdown of scp2 did not interfere with the patterning of the kidney along its proximo-distal axis, but dramatically decreased the size of the kidney, in particular the proximal tubules. This phenotype was accompanied by a reduction of lipid rafts, but was independent of the peroxisomal or transcriptional activities of scp2. Finally, disrupting lipid micro-domains by inhibiting cholesterol synthesis using Mevinolin phenocopied the defects seen in scp2 morphants. Together these data underscore the importance for localized signaling platforms in the proper formation of the Xenopus kidney.
Topics: Animals; Anticholesteremic Agents; Body Patterning; Carrier Proteins; Cell Line; Cholesterol; Gene Knockdown Techniques; HEK293 Cells; Humans; Kidney Tubules, Proximal; Lovastatin; Membrane Microdomains; Morpholinos; RNA, Messenger; Transcription, Genetic; Xenopus Proteins; Xenopus laevis
PubMed: 25127994
DOI: 10.1016/j.ydbio.2014.07.025