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Identification of adult nephron progenitors capable of kidney regeneration in zebrafish


Loss of kidney function underlies many renal diseases1. Mammals can partly repair their nephrons (the functional units of the kidney), but cannot form new ones2,3. By contrast, fish add nephrons throughout their lifespan and regenerate nephrons de novo after injury4,5, providing a model for understanding how mammalian renal regeneration may be therapeutically activated. Here we trace the source of new nephrons in the adult zebrafish to small cellular aggregates containing nephron progenitors. Transplantation of single aggregates comprising 10–30 cells is sufficient to engraft adults and generate multiple nephrons. Serial transplantation experiments to test self-renewal revealed that nephron progenitors are long-lived and possess significant replicative potential, consistent with stem-cell activity. Transplantation of mixed nephron progenitors tagged with either green or red fluorescent proteins yielded some mosaic nephrons, indicating that multiple nephron progenitors contribute to a single nephron. Consistent with this, live imaging of nephron formation in transparent larvae showed that nephrogenic aggregates form by the coalescence of multiple cells and then differentiate into nephrons. Taken together, these data demonstrate that the zebrafish kidney probably contains self-renewing nephron stem/progenitor cells. The identification of these cells paves the way to isolating or engineering the equivalent cells in mammals and developing novel renal regenerative therapies.

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Figure 1: The adult zebrafish kidney undergoes nephrogenesis throughout life and after injury.
Figure 2: The adult zebrafish kidney contains transplantable progenitors that form functional nephrons.
Figure 3: Expression of lhx1a:EGFP and other renal factors in the adult kidney.
Figure 4: lhx1a:EGFP + cells form nephrons during adult kidney development and after transplantation.


  1. Fogo, A. B. Mechanisms of progression of chronic kidney disease. Pediatr. Nephrol. 22, 2011–2022 (2007)

    Article  Google Scholar 

  2. Humphreys, B. D. et al. Intrinsic epithelial cells repair the kidney after injury. Cell Stem Cell 2, 284–291 (2008)

    CAS  Article  Google Scholar 

  3. Hartman, H. A., Lai, H. L. & Patterson, L. T. Cessation of renal morphogenesis in mice. Dev. Biol. 310, 379–387 (2007)

    CAS  Article  Google Scholar 

  4. Reimschuessel, R. A fish model of renal regeneration and development. ILAR J. 42, 285–291 (2001)

    CAS  Article  Google Scholar 

  5. Zhou, W. et al. Characterization of mesonephric development and regeneration using transgenic zebrafish. Am. J. Physiol. Renal Physiol. 299, F1040–F1047 (2010)

    CAS  Article  Google Scholar 

  6. Wingert, R. A. et al. The cdx genes and retinoic acid control the positioning and segmentation of the zebrafish pronephros. PLoS Genet. 3, 1922–1938 (2007)

    CAS  Article  Google Scholar 

  7. Augusto, J., Smith, B., Smith, S., Robertson, J. & Reimschuessel, R. Gentamicin-induced nephrotoxicity and nephroneogenesis in Oreochromis nilotica, a tilapian fish. Dis. Aquat. Organ. 26, 49–58 (1996)

    CAS  Article  Google Scholar 

  8. Kramer-Zucker, A. G., Wiessner, S., Jensen, A. M. & Drummond, I. A. Organization of the pronephric filtration apparatus in zebrafish requires Nephrin, Podocin and the FERM domain protein Mosaic eyes. Dev. Biol. 285, 316–329 (2005)

    CAS  Article  Google Scholar 

  9. Traver, D. et al. Effects of lethal irradiation in zebrafish and rescue by hematopoietic cell transplantation. Blood 104, 1298–1305 (2004)

    CAS  Article  Google Scholar 

  10. Hall, C. et al. Transgenic zebrafish reporter lines reveal conserved Toll-like receptor signaling potential in embryonic myeloid leukocytes and adult immune cell lineages. J. Leukoc. Biol. 85, 751–765 (2009)

    CAS  Article  Google Scholar 

  11. Kobayashi, A. et al. Six2 defines and regulates a multipotent self-renewing nephron progenitor population throughout mammalian kidney development. Cell Stem Cell 3, 169–181 (2008)

    CAS  Article  Google Scholar 

  12. Purton, L. E. & Scadden, D. T. Limiting factors in murine hematopoietic stem cell assays. Cell Stem Cell 1, 263–270 (2007)

    CAS  Article  Google Scholar 

  13. Dressler, G. R. The cellular basis of kidney development. Annu. Rev. Cell Dev. Biol. 22, 509–529 (2006)

    CAS  Article  Google Scholar 

  14. Kobayashi, A. et al. Distinct and sequential tissue-specific activities of the LIM-class homeobox gene Lim1 for tubular morphogenesis during kidney development. Development 132, 2809–2823 (2005)

    CAS  Article  Google Scholar 

  15. Georgas, K. 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. 332, 273–286 (2009)

    CAS  Article  Google Scholar 

  16. Swanhart, L. et al. Characterization of an lhx1a transgenic reporter in zebrafish. Int. J. Dev. Biol. 54, 731–736 (2010)

    CAS  Article  Google Scholar 

  17. Gurdon, J. B. A community effect in animal development. Nature 336, 772–774 (1988)

    ADS  CAS  Article  Google Scholar 

  18. Lee, Y., Grill, S., Sanchez, A., Murphy-Ryan, M. & Poss, K. D. Fgf signaling instructs position-dependent growth rate during zebrafish fin regeneration. Development 132, 5173–5183 (2005)

    CAS  Article  Google Scholar 

  19. Westerfield, M. The Zebrafish Book: A Guide for the Laboratory Use of Zebrafish (Danio rerio) 4th edn (Univ. Oregon Press, 2000)

    Google Scholar 

  20. Perner, B., Englert, C. & Bollig, F. The Wilms tumor genes wt1a and wt1b control different steps during formation of the zebrafish pronephros. Dev. Biol. 309, 87–96 (2007)

    CAS  Article  Google Scholar 

  21. Urasaki, A., Morvan, G. & Kawakami, K. Functional dissection of the tol2 transposable element identified the minimal cis-sequence and a highly repetitive sequence in the subterminal region essential for transposition. Genetics 174, 639–649 (2006)

    CAS  Article  Google Scholar 

  22. Kawakami, K. et al. A transposon-mediated gene trap approach identifies developmentally regulated genes in zebrafish. Dev. Cell 7, 133–144 (2004)

    CAS  Article  Google Scholar 

  23. Elizondo, M. R. et al. Defective skeletogenesis with kidney stone formation in dwarf zebrafish mutant for trpm7 . Curr. Biol. 15, 667–671 (2005)

    CAS  Article  Google Scholar 

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We thank E. C. Liao for help with suturing, and R. Ethier and L. Gyr for zebrafish care. A.J.D. was supported by the Harvard Stem Cell Institute, the American Society of Nephrology and the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (P50DK074030).

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Authors and Affiliations



C.Q.D. and A.J.D. designed the experimental strategy, analysed data, prepared the manuscript, and generated and characterized the Tg(cdh17:EGFP), Tg(cdh17:mCherry) and Tg(wt1b:mCherry) lines. C.Q.D. performed the regeneration, transplants, time course and ablation experiments. C.Q.D., D.M. and R.I.H. made the initial observation that nephron progenitors can be transplanted. N.A.H. generated the Tg(lhx1a:EGFP) line (R01DK069403), F.B. and C.E. generated the Tg(wt1b:EGFP) line, and T.I. and F.O. provided the Tg(pax8:DsRed) line. N.A., R.A.W., G.D. and B.L. analysed kidney expression. H.Z. provided sections of regenerating kidneys. R.C.D., T.M.H., R.W.N., and C.A.C. performed quantitative PCR and microarray analyses. All authors commented on the manuscript.

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Correspondence to Alan J. Davidson.

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The authors declare no competing financial interests.

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Diep, C., Ma, D., Deo, R. et al. Identification of adult nephron progenitors capable of kidney regeneration in zebrafish. Nature 470, 95–100 (2011).

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