Development of the Human Kidney: Immunohistochemical Findings

  • Daniela Fanni
  • Clara Gerosa
  • Peter Van Eyken
  • Yukio Gibo
  • Gavino Faa
Part of the Current Clinical Pathology book series (CCPATH)


The development of the human kidney is a complex process that requires interactions among multiple cell types of different embryological origin, including multipotential/stem cells, epithelial and mesenchymal cells: moreover, all these cell types undergo, during fetal kidney development, multiple steps of cellular differentiation, some of which have not well defined and characterized yet. The coordinate development of multiple highly specialized epithelial, vascular, and stromal cell types is a peculiar feature of the kidney architectural and functional complexity.


Zinc Migration Filtration Lymphoma Leukemia 


  1. 1.
    Dressler GR. The cellular basis of kidney development. Annu Rev Cell Dev Biol. 2006;22:509–29.PubMedCrossRefGoogle Scholar
  2. 2.
    Faa G, Gerosa C, Fanni D, Monga G, Zaffanello M, Van Eyken P, Fanos V. Morphogenesis and molecular mechanisms involved in human kidney development. J Cell Physiol. 2012;227:1257–68.PubMedCrossRefGoogle Scholar
  3. 3.
    Kreidberg JA, Saviola H, Loring JM, Maeda M, Pelletier J, Housman D, Jaenisch R. WT-1 is required for early kidney development. Cell. 1993;74:679–91.PubMedCrossRefGoogle Scholar
  4. 4.
    Gao X, Chen X, Taglienti M, Rumballe B, Little MH, Kreidberg JA. Angioblast mesenchyme induction of early kidney development is mediated by WT1 and Vegfa. Development. 2005;132:5437–49.PubMedCrossRefGoogle Scholar
  5. 5.
    Kreidberg JA. WT1 and kidney progenitor cells. Organogenesis. 2010;6:61–70.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Fanni D, Fanos V, Monga G, Gerosa C, Locci A, Nemolato S, et al. Expression of WT1 during normal human kidney development. J Matern Fetal Neonatal Med. 2011;24 Suppl 2:44–7.PubMedCrossRefGoogle Scholar
  7. 7.
    Hartwig S, Ho J, Pandey P, Maclsaac K, Tagliaenti M, Xiang M, et al. Genomic characterization of Wilms’ tumor suppressor 1 targets in nephron progenitor cells during kidney development. Development. 2010;137: 1189–203.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Faa G, Gerosa C, Fanni D, Nemolato S, Di Felice E, Van Eyken P, et al. The role of immunohistochemistry in the study of the newborn kidney. J Matern Fetal Neonatal Med. 2012;25 Suppl 4:127–30.CrossRefGoogle Scholar
  9. 9.
    Locci G, Gerosa C, Ravarino A, Senes G, Fanni D. CD44 immunoreactivity in diabetic nephropathy and the developing human kidney: a marker of renal progenitor stem cells. JPNIM. 2012;1:138–9.Google Scholar
  10. 10.
    Georgas K, Rumballe B, Valerius MT, Chiu HS, Thiagarajan RD, Lesieur E, et al. Analysis of early nephron patterning reveals a role for distal RV proliferation in fusion to the ureteric tip via a cap mesenchyme-derived connecting segment. Dev Biol. 2009;332:273–86.PubMedCrossRefGoogle Scholar
  11. 11.
    Fanni D, Gerosa C, Nemolato S, Mocci C, Pichiri G, Coni P, et al. “Physiological” renal regenerating medicine in VLBW preterm infants: could a dream come true? J Matern Fetal Neonatal Med. 2012;25 Suppl 3:41–8.PubMedCrossRefGoogle Scholar
  12. 12.
    Sorenson CM. Fulminant metanephric apoptosis and abnormal kidney development in bcl-2-deficient mice. Am J Physiol. 1995;268:F73–81.PubMedGoogle Scholar
  13. 13.
    Korsmeyer SJ. Bcl-2/Bas: a rheostat that regulates an anti-oxidant pathway and cell death. Semin Cancer Biol. 1993;4:327–32.PubMedGoogle Scholar
  14. 14.
    Faa G, Gerosa C, Fanni D, Nemolato S, Di Felice E, Van Eyken P, et al. The role of immunohistochemistry in the study of the newborn kidney. J Matern Fetal Neonatal Med. 2012;25(S4):135–8.PubMedCrossRefGoogle Scholar
  15. 15.
    Di Felice E, Fanni D, Nemolato S, Zurrida V, Murgianu I, Gariel D, Gerosa C. hCTR1 expression in the developing kidney: how copper is involved in human nephrogenesis. JPNIM. 2012;1:120–1.Google Scholar
  16. 16.
    Rumballe B, Georgas K, Wilkinson L, Little M. Molecular anatomy of the kidney: what have we learned from gene expression and functional genomics? Pediatr Nephrol. 2010;25:1005–6.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Fanni D, Fanos V, Monga G, Gerosa C, Nemolato S, Locci A, et al. MUC1 in mesenchymal-to-epithelial transition during human nephrogenesis: changing the fate of renal progenitor/stem cells? J Matern Fetal Neonatal Med. 2011;24 Suppl 2:63–6.PubMedCrossRefGoogle Scholar
  18. 18.
    Fanni D, Iacovidou N, Locci A, Gerosa C, Nemolato S, Van Eyken P, et al. MUC1 marks collecting tubules, renal vesicles, comma- and S-shaped bodies in human developing kidney tubules, renal vesicles, comma- and s-shaped bodies in human kidney. Eur J Histochem. 2012;56:e40. doi: 10.4081/ejh.2012.e40.PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Faa G, Gerosa C, Fanni D, Nemolato S, Marinelli V, Locci A, et al. CD10 in the developing human kidney: immunoreactivity and possible role in renal embryogenesis. J Matern Fetal Neonatal Med. 2012;25:904–11.PubMedCrossRefGoogle Scholar
  20. 20.
    Gerosa C, Fanni D, Puxeddu E, Piludu M, Piras M, Furno M, Faa G, Fanos V. Perinatal programming and the kidney: how can immunohistochemistry and electron microscopy improve our knowledge? Acta Med Port. 2012;25(S2):121–8.Google Scholar
  21. 21.
    Fatima H, Moeller MJ, Smeets B, Yang H-C, Fogo AB. Parietal epithelial cell activation distinguishes early recurrence of FSGS in the transplant from minimal change disease. Mod Pathol. 2011;24(S1):344A.Google Scholar
  22. 22.
    Nemolato S, Cabras T, Fanari MU, Cau F, Fanni D, Gerosa C, et al. Immunoreactivity of thymosin beta 4 in human foetal and adult genitourinary tract. Eur J Histochem. 2010;54(4):e43.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Coni P, Nemolato S, Di Felice E, Sanna A, Ottonello G, Cabras T, et al. Thymosin beta-4 translocation from the trans-Golgi network to the nucleus in kidney proximal tubule cell line LLC-PK1 under starvation. J Matern Fetal Neonatal Med. 2012;1:119–20.Google Scholar
  24. 24.
    Cannas AR, Deiana R, Milia MA, Muscas B, Paderi S, Serra S, et al. PAS and Weigert methods: two old stains for a new interpretation of the newborn kidney [abstract]. J Pediatr Neonatal Individualized Med. 2012;1:139.Google Scholar
  25. 25.
    Faa G, Gerosa C, Fanni D, Nemolato S, Monga G, Fanos V. Kidney embryogenesis: how to look at old things with new eyes. In: Fanos V, Chevalier RL, Faa G, Cataldi L, editors. Developmental nephrology: from embryology to metabolomics. Quartu Sant’Elena: Hygeia Press; 2011. p. 23–45.Google Scholar
  26. 26.
    Eremina V, Baelde HJ, Quaggin SE. Role of VEGF-a signaling pathway in the glomerulus: evidence for crosstalk between components of the glomerular filtration barrier. Nephron Physiol. 2007;106:32–7.CrossRefGoogle Scholar
  27. 27.
    Fonseca Ferraz ML, Dos Santos AM, Cavellani CL, Rossi RC, Correa RR, Dos Reis MA, de Paula Antunes Teixeira V, da Cunha Castro EC. Histochemical and immunohistochemical study of the glomerular development in human fetuses. Pediatr Nephrol. 2008;23:257–62.PubMedCrossRefGoogle Scholar
  28. 28.
    Kobayashi A, Valerius MT, Mugford JW, Carroll TJ, Self M, Oliver J, McMahon AP. Six2 defines and regulates a multipotent self-renewing nephron progenitor population throughout mammalian kidney development. Cell Stem Cell. 2008;3:169–81.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Masuya M, Drake CJ, Fleming PA, Reilly CM, Zeng H, Hill WD, Martin-Studdard A, Hess DC, Ogawa M. Hematopoietic origin of glomerular mesangial cells. Blood. 2003;101:2215–8.PubMedCrossRefGoogle Scholar
  30. 30.
    Abe T, Fleming PA, Masuya M, Minamiguchi H, Drake CJ, Ogawa M. Granulocyte/macrophage origin of glomerular mesangial cells. Int J Hematol. 2005;82:115–8.PubMedCrossRefGoogle Scholar
  31. 31.
    Wellik D. HOX genes and kidney development. Pediatr Nephrol. 2011;26:1559–65.PubMedCrossRefGoogle Scholar
  32. 32.
    Boor P, Floege J. The renal (myo-)fibroblast: a heterogeneous group of cells. Nephrol Dial Transplant. 2012;27:3027–36.PubMedCrossRefGoogle Scholar
  33. 33.
    Goodpaster T, Legesse-Miller A, Hameed MR, Aisner SC, Randolph-Habecker J, Coller HA. An immunohistochemical method for identifying fibroblasts in formalin-fixed, paraffin-embedded tissue. J Histochem Cytochem. 2008;56:347–58.PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    McAnulty RJ. Fibroblasts and myofibroblasts: their source, function and role in disease. Int J Biochem Cell Biol. 2007;39:666–7.PubMedGoogle Scholar
  35. 35.
    Oliver JA, Maarouf O, Cheema FH, Martens TP, Al-Awqati Q. The renal papilla is a niche for adult kidney stem cells. J Clin Invest. 2004;114:795–804.PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Trowe MO, Airik R, Weiss AC, Farin HF, Foik AB, Bettenhausen E, Schuster-Gossler K, Taketo MM, Kispert A. Canonical Wnt signaling regulates smooth muscle precursor development in the mouse ureter. Development. 2012;139:3099–108.PubMedCrossRefGoogle Scholar
  37. 37.
    Airik R, Trowe MO, Foik A, Farin HF, Petry M, Schuster-Gossler K, Schweizer M, Scherer G, Kist R, Kispert A. Hydroureteronephrosis due to loss of Sox9-regulated smooth muscle cell differentiation of the ureteric mesenchyme. Hum Mol Genet. 2010;19: 4918–29.PubMedCrossRefGoogle Scholar
  38. 38.
    Herzlinger D. The pelvis-kidney junction contains HCN3 a hyperpolarization-activated cation channel that triggers ureter peristalsis. In: 11th international workshop on developmental nephrology, August 24–27. New Paltz: Oral Presentation O-35; 2010.Google Scholar
  39. 39.
    Kuvel M, Canguven O, Murtazaoglu M, Albayrak S. Distribution of Cajal like cells and innervation in intrinsic ureteropelvic junction obstruction. Arch Ital Urol Androl. 2011;83:128–32.PubMedGoogle Scholar
  40. 40.
    Chevalier RL. Obstructive uropathy: state of the art. In: Fanos V, Chevalier RL, Faa G, Cataldi L, editors. Developmental nephrology: from embryology to metabolomics. Quartu Sant’Elena: Hygeia Press; 2011. p. 47–56.Google Scholar
  41. 41.
    Little MH, Brennan J, Georgas K, et al. A high resolution anatomical ontology of the developing murine genitourinary tract. Gene Expr Patterns. 2007;7: 680–99.PubMedCentralPubMedCrossRefGoogle Scholar
  42. 42.
    Kurtz L, Madsen K, Kurt B, Jensen BL, Walter S, Banas B, Wagner C, Kurtz A. High-level connexin expression in the human juxtaglomerular apparatus. Nephron Physiol. 2010;116:1–8.CrossRefGoogle Scholar
  43. 43.
    Kurtz L, Schweda F, de Wit C, Kriz W, Witzgall R, Warth R, Sauter A, Kurtz A, Wagner C. Lack of connexin 40 causes displacement of renin-producing cells from afferent arterioles to the extraglomerular mesangium. J Am Soc Nephrol. 2007;18(4):1103–11.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Daniela Fanni
    • 1
  • Clara Gerosa
    • 1
  • Peter Van Eyken
    • 2
  • Yukio Gibo
    • 3
  • Gavino Faa
    • 4
    • 5
  1. 1.Department of Surgical Sciences, Division of PathologyUniversity of CagliariCagliariItaly
  2. 2.Department of PathologyZiekenhuis Oost-LimburgGenkBelgium
  3. 3.Hepatology ClinicMatsumotoJapan
  4. 4.Department of Surgical Sciences, Institute of PathologyAzienda Ospedaliera Universitaria and University of CagliariCagliariItaly
  5. 5.Temple UniversityPhiladelphiaUSA

Personalised recommendations