Abstract
Medaka has a pronephros at early larval stages, and thereafter the mesonephros develops in the tissues around the pronephric tubule and duct. A marked increase in mesonephric nephrons continues until 2 to 3 months after hatching, and consequently the mesonephros consists of 200–300 nephrons on each side. The nephrogenic processes can be histologically featured in the developing mesonephros as three distinguishable stages: mesenchymal condensation, formation of a nephrogenic body, and maturation of the nephron. The appearance of mesenchymal condensates and nephrogenic bodies in the interstitial tissue indicates that the de novo nephrogenesis takes place actively. As these nephron precursors are positive for wt1 expression, wt1 could be a good marker of de novo nephrogenesis.
The program for nephron development can be reactivated in medaka during adulthood by artificial injury with chemicals. Intraperitoneal administration of gentamicin, damaging tubules, ducts, and the glomeruli, leads to a significant increase of the mesenchymal condensates and nephrogenic bodies in the injured kidney, which can be also recognized as wt1-positive cell masses. Thus, in contrast to mammals, medaka is capable of regenerating the kidney through de novo nephrogenesis, possibly by recruiting stem cells retained in the interstitial tissue of the adult kidney.
The medaka pc mutant shows lesions quite similar to those of the human genetic disease polycystic kidney disease (PKD): it develops numerous fluid-filled renal cysts and suffers from enlargement of the abdomen. Genetic linkage analysis identified the causative gene to be the medaka ortholog of glis3. In humans, the mutations in GLIS3 have been reported to be involved in pathogenesis of pleiotropic genetic diseases including PKD and diabetes. Consistent with the medaka mutant phenotype, glis3 mRNA is expressed in the epithelia of the renal tubule and duct. The cilia in the pronephric tubule are significantly shortened in the pc mutant. Glis3 protein is preferentially located in the cilium of renal epithelial cell. Similar to the other PKD genes reported previously, glis3 may also play a crucial role in the ciliary structure or function.
All the findings suggest that medaka serves as a good model for understanding the process of kidney development and regeneration as well as the pathogenesis of human genetic kidney diseases.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Bisgrove BW, Yost HJ (2006) The roles of cilia in developmental disorders and disease. Development (Camb) 133:4131–4143
Cantley LG (2005) Adult stem cells in the repair of the injured renal tubule. Nat Clin Pract Nephrol 1:22–32
Chauvet V, Tian X, Husson H, Grimm DH, Wang T, Hiesberger T, Igarashi P, Bennett AM, Ibraghimov-Beskrovnaya O, Somlo S, Caplan MJ (2004) Mechanical stimuli induce cleavage and nuclear translocation of the polycystin-1 C terminus. J Clin Invest 114:1433–1443
Cormier SM, Neiheisel TW, Racine RN, Reimschussel R (1995) New nephron development in fish from polluted waters: a possible biomarker. Ecotoxicology 4:157–168
Drummond I (2003) The skate weighs in on kidney regeneration. J Am Soc Nephrol 14:1704–1705
Drummond IA, Majumdar A, Hentschel H, Elger M, Solnica-Krezel L, Schier AF, Neuhauss SC, Stemple DL, Zwartkruis F, Rangini Z, Driever W, Fishman MC (1998) Early development of the zebrafish pronephros and analysis of mutations affecting pronephric function. Development (Camb) 125:4655–4667
Elger M, Hentschel H, Litteral J, Wellner M, Kirsch T, Luft FC, Haller H (2003) Nephrogenesis is induced by partial nephrectomy in the elasmobranch Leucoraja erinacea. J Am Soc Nephrol 14:1506–1518
Fedorova S, Miyamoto R, Harada T, Isogai S, Hashimoto H, Ozato K, Wakamatsu Y (2008) Renal glomerulogenesis in medaka fish, Oryzias latipes. Dev Dyn 237:2342–2352
Gilbert SF (2003) Developmental biology. Sinauer, Sunderland
Harder W (1975) Anatomy of fishes. Schweizerbart, Stuttgart
Hickman CPJ, Trump BF (1969) The kidney. In: Hoar WS, Randall DJ (eds) Fish physiology. Academic Press, New York, pp 91–239
Igarashi P, Somlo S (2002) Genetics and pathogenesis of polycystic kidney disease. J Am Soc Nephrol 13:2384–2398
Igarashi P, Somlo S (2007) Polycystic kidney disease. J Am Soc Nephrol 18:1371–1373
Kang HS, Beak JY, Kim YS, Herbert R, Jetten AM (2009) Glis3 is associated with primary cilia and Wwtr1/TAZ and implicated in polycystic kidney disease. Mol Cell Biol 29:2556–2569
Karp R, Brasel JA, Winick M (1971) Compensatory kidney growth after uninephrectomy in adult and infant rats. Am J Dis Child 121:186–188
Kim YS, Lewandoski M, Perantoni AO, Kurebayashi S, Nakanishi G, Jetten AM (2002) Identification of Glis1, a novel Gli-related, Kruppel-like zinc finger protein containing transactivation and repressor functions. J Biol Chem 277:30901–30913
Kim YS, Nakanishi G, Lewandoski M, Jetten AM (2003) GLIS3, a novel member of the GLIS subfamily of Kruppel-like zinc finger proteins with repressor and activation functions. Nucleic Acids Res 31:5513–5525
Kim SC, Kim YS, Jetten AM (2005) Kruppel-like zinc finger protein Gli-similar 2 (Glis2) represses transcription through interaction with C-terminal binding protein 1 (CtBP1). Nucleic Acids Res 33:6805–6815
Kramer-Zucker AG, Olale F, Haycraft CJ, Yoder BK, Schier AF, Drummond IA (2005) Cilia-driven fluid flow in the zebrafish pronephros, brain and Kupffer’s vesicle is required for normal organogenesis. Development (Camb) 132:1907–1921
Kreidberg JA, Sariola H, Loring JM, Maeda M, Pelletier J, Housman D, Jaenisch R (1993) WT-1 is required for early kidney development. Cell 74:679–691
Lagler KF, Bardach JE, Miller RR, May Passino DR (1977) Ichthyology. Wiley, New York
Lin F, Moran A, Igarashi P (2005) Intrarenal cells, not bone marrow-derived cells, are the major source for regeneration in postischemic kidney. J Clin Invest 115:1756–1764
Mochizuki E, Fukuta K, Tada T, Harada T, Watanabe N, Matsuo S, Hashimoto H, Ozato K, Wakamatsu Y (2005) Fish mesonephric model of polycystic kidney disease in medaka (Oryzias latipes) pc mutant. Kidney Int 68:23–34
Nauli SM, Zhou J (2004) Polycystins and mechanosensation in renal and nodal cilia. BioEssays 26:844–856
Nauli SM, Alenghat FJ, Luo Y, Williams E, Vassilev P, Li X, Elia AE, Lu W, Brown EM, Quinn SJ, Ingber DE, Zhou J (2003) Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nat Genet 33:129–137
Omran H, Kobayashi D, Olbrich H, Tsukahara T, Loges NT, Hagiwara H, Zhang Q, Leblond G, O’Toole E, Hara C, Mizuno H, Kawano H, Fliegauf M, Yagi T, Koshida S, Miyawaki A, Zentgraf H, Seithe H, Reinhardt R, Watanabe Y, Kamiya R, Mitchell DR, Takeda H (2008) Ktu/PF13 is required for cytoplasmic pre-assembly of axonemal dyneins. Nature (Lond) 456:611–616
Perner B, Englert C, Bollig F (2007) The Wilms tumor genes wt1a and wt1b control different steps during formation of the zebrafish pronephros. Dev Biol 309:87–96
Reimschuessel R (2001) A fish model of renal regeneration and development. ILAR J 42:285–291
Reimschuessel R, Biggs K (1996) Zebrafish model for nephron regeneration following injury. Cold Spring Harbor Symposium on Zebrafish Development and Genetics. Cold Spring Harbor, New York
Reimschuessel R, Bennett RO, May EB, Lipsky MM (1990) Development of newly formed nephrons in the goldfish kidney following hexachlorobutadiene-induced nephrotoxicity. Toxicol Pathol 18:32–38
Reimschuessel R, Bennett RO, May EA, Lipsky MM (1993) Pathological alterations and new nephron development in rainbow trout Oncorhynchus mykiss following tetrachloroethylene contamination. J Zoo Anim Med 24:503–507
Ricardo SD, Deane JA (2005) Adult stem cells in renal injury and repair. Nephrology (Carlton) 10:276–282
Rookmaaker MB, Smits AM, Tolboom H, Van’t Wout K, Martens AC, Goldschmeding R, Joles JA, Van Zonneveld AJ, Grone HJ, Rabelink TJ, Verhaar MC (2003) Bone-marrow-derived cells contribute to glomerular endothelial repair in experimental glomerulonephritis. Am J Pathol 163:553–562
Salice CJ, Rokous JS, Kane AS, Reimschuessel R (2001) New nephron development in goldfish (Carassius auratus) kidneys following repeated gentamicin-induced nephrotoxicosis. Comp Med 51:56–59
Senee V, Chelala C, Duchatelet S, Feng D, Blanc H, Cossec JC, Charon C, Nicolino M, Boileau P, Cavener DR, Bougneres P, Taha D, Julier C (2006) Mutations in GLIS3 are responsible for a rare syndrome with neonatal diabetes mellitus and congenital hypothyroidism. Nat Genet 38:682–687
Serluca FC, Fishman MC (2001) Pre-pattern in the pronephric kidney field of zebrafish. Development (Camb) 128:2233–2241
Taulman PD, Haycraft CJ, Balkovetz DF, Yoder BK (2001) Polaris, a protein involved in left-right axis patterning, localizes to basal bodies and cilia. Mol Biol Cell 12:589–599
Tobin JL, Beales PL (2007) Bardet–Biedl syndrome: beyond the cilium. Pediatr Nephrol 22:926–936
Vainio S, Lin Y (2002) Coordinating early kidney development: lessons from gene targeting. Nat Rev Genet 3:533–543
Verghese E, Weidenfeld R, Bertram JF, Ricardo SD, Deane JA (2008) Renal cilia display length alterations following tubular injury and are present early in epithelial repair. Nephrol Dial Transplant 23:834–841
Wang S, Luo Y, Wilson PD, Witman GB, Zhou J (2004) The autosomal recessive polycystic kidney disease protein is localized to primary cilia, with concentration in the basal body area. J Am Soc Nephrol 15:592–602
Watanabe N, Kato M, Suzuki N, Inoue C, Fedorova S, Hashimoto H, Maruyama S, Matsuo S, Wakamatsu Y (2009) Kidney regeneration through nephron neogenesis in medaka. Dev Growth Differ 51:135–143
Watnick T, Germino G (2003) From cilia to cyst. Nat Genet 34:355–356
Yoder BK (2007) Role of primary cilia in the pathogenesis of polycystic kidney disease. J Am Soc Nephrol 18:1381–1388
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2011 Springer
About this chapter
Cite this chapter
Hashimoto, H. (2011). Kidney Development, Regeneration, and Polycystic Kidney Disease in Medaka. In: Naruse, K., Tanaka, M., Takeda, H. (eds) Medaka. Springer, Tokyo. https://doi.org/10.1007/978-4-431-92691-7_8
Download citation
DOI: https://doi.org/10.1007/978-4-431-92691-7_8
Publisher Name: Springer, Tokyo
Print ISBN: 978-4-431-92690-0
Online ISBN: 978-4-431-92691-7
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)