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Developmental Biology Aug 1997Most vertebrate organs, once formed, continue to perform the function for which they were generated until the death of the organism. The kidney is a notable exception to... (Review)
Review
Most vertebrate organs, once formed, continue to perform the function for which they were generated until the death of the organism. The kidney is a notable exception to this rule. Vertebrates, even those that do not undergo metamorphosis, utilize a progression of more complex kidneys as they grow and develop. This is presumably due to the changing conditions to which the organism must respond to retain what Homer Smith referred to as our physiological freedom. To quote, "Recognizing that we have the kind of blood we have because we have the kind of kidneys we have, we must acknowledge that our kidneys constitute the major foundation of our physiological freedom. Only because they work the way they do has it become possible for us to have bones, muscles, glands, and brains. Superficially, it might be said that the function of the kidneys is to make urine; but in a more considered view one can say that the kidneys make the stuff of philosophy itself" ("From Fish to Philosopher," Little, Brown and Co., Boston, 1953). Different kidneys are used to make the stuff of philosophy at different stages of development depending on the age and needs of the organism, rather than the usual approach of simply making embryonic organs larger as the animal grows. Although evolution has provided the higher vertebrates with complex adult kidneys, they continue to utilize simple kidneys in embryogenesis. In lower vertebrates with simple adult kidneys, even more simple versions are used during early developmental stages. In this review the anatomy, development, and gene expression patterns of the embryonic kidney, the pronephros, will be described and compared to the more complex kidney forms. Despite some differences in anatomy, similar developmental pathways seem to be responsible for the induction and the response to induction in both evanescent and permanent kidney forms. Gene expression patterns can, therefore, be added to the morphological and functional data indicating that all forms of the kidney are closely related structures. Given the similarities between the development of simple and complex kidneys, the embryonic kidneys may be an ideal model system in which to investigate the genesis of multicomponent organ systems.
Topics: Animals; Embryonic Induction; Embryonic and Fetal Development; Gene Expression Regulation, Developmental; Humans; Kidney; Mutation; Vertebrates
PubMed: 9268568
DOI: 10.1006/dbio.1997.8629 -
PloS One 2013Bardet-Biedl syndrome (BBS) and nephronophthisis (NPH) are hereditary autosomal recessive disorders, encoded by two families of diverse genes. BBS and NPH display...
Bardet-Biedl syndrome (BBS) and nephronophthisis (NPH) are hereditary autosomal recessive disorders, encoded by two families of diverse genes. BBS and NPH display several overlapping phenotypes including cystic kidney disease, retinitis pigmentosa, liver fibrosis, situs inversus and cerebellar defects. Since most of the BBS and NPH proteins localize to cilia and/or their appendages, BBS and NPH are considered ciliopathies. In this study, we characterized the function of the transcription factor Nphp7 in zebrafish, and addressed the molecular connection between BBS and NPH. The knockdown of zebrafish bbs1 and nphp7.2 caused similar phenotypic changes including convergent extension defects, curvature of the body axis, hydrocephalus, abnormal heart looping and cystic pronephros, all consistent with an altered ciliary function. Immunoprecipitation assays revealed a physical interaction between BBS1 and NPHP7, and the simultaneous knockdown of zbbs1 and znphp7.2 enhanced the cystic pronephros phenotype synergistically, suggesting a genetic interaction between zbbs1 and znphp7.2 in vivo. Deletion of zBbs1 or zNphp7.2 did not compromise cilia formation, but disrupted cilia motility. Although NPHP7 has been shown to act as transcriptional repressor, our studies suggest a crosstalk between BBS1 and NPHP7 in regulating normal function of the cilium.
Topics: Animals; Cilia; Nuclear Proteins; Protein Binding; Zebrafish; Zebrafish Proteins
PubMed: 24069149
DOI: 10.1371/journal.pone.0072549 -
Knockdown of ttc26 disrupts ciliogenesis of the photoreceptor cells and the pronephros in zebrafish.Molecular Biology of the Cell Aug 2012In our effort to understand genetic disorders of the photoreceptor cells of the retina, we have focused on intraflagellar transport in photoreceptor sensory cilia. From...
In our effort to understand genetic disorders of the photoreceptor cells of the retina, we have focused on intraflagellar transport in photoreceptor sensory cilia. From previous mouse proteomic data we identified a cilia protein Ttc26, orthologue of dyf-13 in Caenorhabditis elegans, as a target. We localized Ttc26 to the transition zone of photoreceptor and to the transition zone of cilia in cultured murine inner medullary collecting duct 3 (mIMCD3) renal cells. Knockdown of Ttc26 in mIMCD3 cells produced shortened and defective primary cilia, as revealed by immunofluorescence and scanning electron microscopy. To study Ttc26 function in sensory cilia in vivo, we utilized a zebrafish vertebrate model system. Morpholino knockdown of ttc26 in zebrafish embryos caused ciliary defects in the pronephric kidney at 27 h postfertilization and distension/dilation of pronephros at 5 d postfertilization (dpf). In the eyes, the outer segments of photoreceptor cells appeared shortened or absent, whereas cellular lamination appeared normal in retinas at 5 dpf. This suggests that loss of ttc26 function prevents normal ciliogenesis and differentiation in the photoreceptor cells, and that ttc26 is required for normal development and differentiation in retina and pronephros. Our studies support the importance of Ttc26 function in ciliogenesis and suggest that screening for TTC26 mutations in human ciliopathies is justified.
Topics: Animals; Cell Line; Cilia; Gene Knockdown Techniques; Larva; Male; Mice; Morpholinos; Phenotype; Photoreceptor Cells; Pronephros; Protein Transport; RNA Interference; Rats; Zebrafish; Zebrafish Proteins
PubMed: 22718903
DOI: 10.1091/mbc.E12-01-0019 -
Gene Expression Patterns : GEP Nov 2014The kidney is comprised of nephrons - epithelial tubes with specialized segments that reabsorb and secrete solutes, perform osmoregulation, and produce urine. Different...
The kidney is comprised of nephrons - epithelial tubes with specialized segments that reabsorb and secrete solutes, perform osmoregulation, and produce urine. Different nephron segments exhibit unique combinations of ion channels, transporter proteins, and cell junction proteins that govern permeability between neighboring cells. The zebrafish pronephros is a valuable model to study the mechanisms of vertebrate nephrogenesis, but many basic features of segment gene expression in renal progenitors and mature nephrons have not been characterized. Here, we analyzed the temporal and spatial expression pattern of tight junction components during zebrafish kidney ontogeny. During nephrogenesis, renal progenitors show discrete expression domains of claudin (cldn) 15a, cldn8, occludin (ocln) a, oclnb, tight junction protein (tjp) 2a, tjp2b, and tjp3. Interestingly, transcripts encoding these genes exhibit dynamic spatiotemporal domains during the time when pronephros segment domains are established. These data provide a useful gene expression map of cell junction components during zebrafish nephrogenesis. As such, this information complements the existing molecular map of nephron segment characteristics, and can be used to characterize kidney development mutants as well as various disease models, in addition to aiding in the elucidation of mechanisms governing epithelial regeneration after acute nephron injury.
Topics: Animals; Gene Expression Regulation, Developmental; In Situ Hybridization; Nephrons; Organogenesis; Pronephros; Tight Junctions; Transcription, Genetic; Zebrafish; Zebrafish Proteins
PubMed: 25460834
DOI: 10.1016/j.gep.2014.11.001 -
Cell Cycle (Georgetown, Tex.) Oct 2019Zebrafish erythropoietin a (epoa) is a well characterized regulator of red blood cell formation. Recent morpholino mediated knockdown data have also identified being...
Zebrafish erythropoietin a (epoa) is a well characterized regulator of red blood cell formation. Recent morpholino mediated knockdown data have also identified being essential for physiological pronephros development in zebrafish, which is driven by blocking apoptosis in developing kidneys. Yet, zebrafish mutants for have not been described so far. In order to compare a transient knockdown vs. permanent knockout for in zebrafish on pronephros development, we used CRISPR/Cas9 technology to generate knockout zebrafish mutants and we performed structural and functional studies on pronephros development. In contrast to morphants, zebrafish mutants showed normal pronephros structure; however, a previously uncharacterized gene in zebrafish, named , was identified and upregulated in mutants. knockdown altered pronephros development, which was further aggravated in mutants. Likewise, and morphants regulated similar and differential gene signatures related to kidney development in zebrafish. In conclusion, stable loss of during embryonic development can be compensated by leading to phenotypical discrepancies in knockdown and knockout zebrafish embryos.
Topics: Animals; CRISPR-Cas Systems; Embryo, Nonmammalian; Erythropoietin; Gene Expression Regulation, Developmental; Gene Knockdown Techniques; Gene Knockout Techniques; Heterozygote; Homozygote; Microscopy, Electron; Morpholinos; Organogenesis; Pronephros; Recombinant Proteins; Zebrafish; Zebrafish Proteins
PubMed: 31451030
DOI: 10.1080/15384101.2019.1656019 -
Biology Open Jun 2017Senescence represents a mechanism to avoid undesired cell proliferation that plays a role in tumor suppression, wound healing and embryonic development. In order to gain...
Senescence represents a mechanism to avoid undesired cell proliferation that plays a role in tumor suppression, wound healing and embryonic development. In order to gain insight on the evolution of senescence, we looked at its presence in developing axolotls (urodele amphibians) and in zebrafish (teleost fish), which are both anamniotes. Our data indicate that cellular senescence is present in various developing structures in axolotls (pronephros, olfactory epithelium of nerve fascicles, lateral organs, gums) and in zebrafish (epithelium of the yolk sac and in the lower part of the gut). Senescence was particularly associated with transient structures (pronephros in axolotls and yolk sac in zebrafish) suggesting that it may play a role in the elimination of these tissues. Our data supports the notion that cellular senescence evolved early in vertebrate evolution to influence embryonic development.
PubMed: 28500032
DOI: 10.1242/bio.025809 -
Journal of Anatomy Jul 1920
PubMed: 17103905
DOI: No ID Found -
Frontiers in Immunology 2020Macrophages play important roles in conditions ranging from host immune defense to tissue regeneration and polarize their functional phenotype accordingly. Next to...
Macrophages play important roles in conditions ranging from host immune defense to tissue regeneration and polarize their functional phenotype accordingly. Next to differences in the use of L-arginine and the production of different cytokines, inflammatory M1 macrophages and anti-inflammatory M2 macrophages are also metabolically distinct. In mammals, M1 macrophages show metabolic reprogramming toward glycolysis, while M2 macrophages rely on oxidative phosphorylation to generate energy. The presence of polarized functional immune phenotypes conserved from mammals to fish led us to hypothesize that a similar metabolic reprogramming in polarized macrophages exists in carp. We studied mitochondrial function of M1 and M2 carp macrophages under basal and stressed conditions to determine oxidative capacity by real-time measurements of oxygen consumption and glycolytic capacity by measuring lactate-based acidification. In M1 macrophages, we found increased nitric oxide production and expression in addition to altered oxidative phosphorylation and glycolysis. In M2 macrophages, we found increased arginase activity, and both oxidative phosphorylation and glycolysis were similar to control macrophages. These results indicate that M1 and M2 carp macrophages show distinct metabolic signatures and indicate that metabolic reprogramming may occur in carp M1 macrophages. This immunometabolic reprogramming likely supports the inflammatory phenotype of polarized macrophages in teleost fish such as carp, similar to what has been shown in mammals.
Topics: Animals; Arginase; Carboxy-Lyases; Carps; Cell Polarity; Cyclic AMP; Gene Expression; Glycolysis; Head Kidney; Lipopolysaccharides; Macrophage Activation; Macrophages; Mitochondria; Nitric Oxide; Oxidative Phosphorylation; Phenotype; Transcriptome
PubMed: 32158446
DOI: 10.3389/fimmu.2020.00152 -
Frontiers in Immunology 2021(Cymothoidea, Isopoda) is a generalist crustacean parasite that negatively affects the economic sustainability of European sea bass () aquaculture in the North-East...
(Cymothoidea, Isopoda) is a generalist crustacean parasite that negatively affects the economic sustainability of European sea bass () aquaculture in the North-East Mediterranean. While mortalities are observed in fry and fingerlings, infection in juvenile and adult fish result in approximately 20% growth delay. A transcriptomic analysis (PCR array, RNA-Seq) was performed on organs (tongue, spleen, head kidney, and liver) from infected vs. -free sea bass fingerlings. Activation of local and systemic immune responses was detected, particularly in the spleen, characterized by the upregulation of cytokines (also in the tongue), a general reshaping of the immunoglobulin (Ig) response and suppression of T-cell mediated responses. Interestingly, starvation and iron transport and metabolism genes were strongly downregulated, suggesting that the parasite feeding strategy is not likely hematophagous. The regulation of genes related to growth impairment and starvation supported the growth delay observed in infected animals. Most differentially expressed (DE) transcripts were exclusive of a specific organ; however, only in the tongue, the difference between infected and uninfected fish was significant. At the attachment/feeding site, the pathways involved in muscle contraction and intercellular junction were the most upregulated, whereas the pathways involved in fibrosis (extracellular matrix organization, collagen formation, and biosynthesis) were downregulated. These results suggest that parasite-inflicted damage is successfully mitigated by the host and characterized by regenerative processes that prevail over the reparative ones.
Topics: Animals; Bass; Cytokines; Fish Diseases; Gene Expression Profiling; Head Kidney; Isopoda; Liver; Mediterranean Sea; Parasitic Diseases, Animal
PubMed: 33777043
DOI: 10.3389/fimmu.2021.645607 -
American Journal of Physiology. Renal... May 2021Developing organisms need to adapt to environmental variations as well as to rapid changes in substrate availability and energy demands imposed by fast-growing tissues...
Developing organisms need to adapt to environmental variations as well as to rapid changes in substrate availability and energy demands imposed by fast-growing tissues and organs. Little is known about the adjustments that kidneys undergo in response to these challenges. We performed single-cell RNA sequencing of zebrafish pronephric duct cells to understand how the developing kidney responds to changes in filtered substrates and intrinsic energy requirements. We found high levels of glucose transporters early in development and increased expression of monocarboxylate transporters at later times. This indicates that the zebrafish embryonic kidney displays a high glucose transporting capacity during early development, which is replaced by the ability to absorb monocarboxylates and amino acids at later stages. This change in transport capacity was accompanied by the upregulation of mitochondrial carriers, indicating a switch to increased oxidative phosphorylation to meet the increasing energy demand of a developing kidney. The zebrafish embryonic kidney has high levels of glucose transporters during early development, which are replaced by monocarboxylate and amino acid transporters later on. Inhibition of Na-glucose cotransporter-dependent glucose transport by sotagliflozin also increased expression, supporting the idea that the glucose transport capacity is dynamically adjusted during zebrafish pronephros development. Concurrent upregulation of mitochondrial SCL25 transporters at later stages supports the idea that the pronephros adjusts to changing substrate supplies and/or energy demands during embryonic development.
Topics: Animals; Energy Metabolism; Gene Expression Profiling; Gene Expression Regulation, Developmental; Pronephros; RNA, Messenger; RNA-Seq; Single-Cell Analysis; Solute Carrier Proteins; Transcriptome; Zebrafish; Zebrafish Proteins
PubMed: 33749326
DOI: 10.1152/ajprenal.00610.2020