Kidney Development


Mammals produce three pairs of kidneys: the pronephros and mesonephros are discarded during fetal life whereas the metanephros remains as the permanent excretory organ. It forms when two progenitor tissues – ureteric bud and metanephrogenic mesenchyme – meet and exchange signals. These signals cause the bud to branch repeatedly to form the urinary collecting duct system and cause the mesenchyme to create a stem cell population, and elements of that population to differentiate into excretory nephrons and supporting cells. Further exchanges of signals control endothelial invasion to make the blood system, and the process of innervation. They act by linking to cellular morphogenetic effectors. Many important questions about renal development remain unanswered; some are listed in this article.

Key Concepts:

  • Development of the permanent mammalian kidney (metanephros) occurs almost autonomously, so that even a kidney rudiment in culture, isolated from the rest of the embryo, will develop most of the anatomical features of a normal fetal kidney (but not vascularisation or innervation). The ability to build a kidney is therefore largely a property of the 2–3 cell types present in the rudiment.

  • The precise anatomy of the kidney, like many other organs, is flexible and responsive to environmental influences (mechanical, chemical and hormonal): its general layout may be specified genetically but its microarchitecture is not.

  • Elements of the kidney develop in a specific order: in any given part of the kidney, the collecting duct system, which defines the renal architecture, begins to develop first. Nephrons develop next, with the blood and nervous systems following so that they connect to the nephrons already present. Development continues centrifugally, so that the outer part of the kidney is (until development ceases near birth) still undergoing ‘early’ events, for example, nephron induction, while the central core is much more mature.

  • Kidney development depends on, and is coordinated by, the exchange of signals between cells that regulate motility, proliferation, survival and differentiation.

  • Genetic defects in signalling pathways or in the effector systems that they should trigger result in a significant fraction of common human congenital abnormalities. Mechanical defects in the rest of the embryo can also cause congenital renal defects.

  • The kidney does contain stem cells even after the development has completed, but its capacity for regeneration is limited.

  • There is a major, freely accessible database for urogenital development –

Keywords: metanephros; stem cell; ureteric bud; signalling; organogenesis

Figure 1.

Stages in nephron development: these images are of mouse metanephroi stained for the basement protein, laminin.

Figure 2.

A diagrammatic representation of a mature nephron, showing the sequence of structures along the proximodistal axis from glomerulus to distal tubule, and also the arrangement of the blood system.

Figure 3.

Gene networks involved in controlling the balance between cap mesenchyme stem cell maintenance or differentiation. The box marked ‘UB tip’ represents the tip of the ureteric bud, whereas the box marked ‘cap mesenchyme’ represents the stem cell compartment. The arrows in the networks imply regulation but not necessarily direct regulation. Current knowledge of this network remains incomplete: even less is known about the networks in other renal cell types.



Bates CM (2007) Role of fibroblast growth factor receptor signaling in kidney development. Pediatric Nephrology 22: 343–349.

Broughton Pipkin F , Kirkpatrick SM , Lumbers ER and Mott JC (1974) Renin and angiotensin‐like levels in foetal, new‐born and adult sheep. Journal of Physiology 241: 575–588.

Carroll TJ , Park JS , Hayashi S , Majumdar A and McMahon AP (2005) Wnt9b plays a central role in the regulation of mesenchymal to epithelial transitions underlying organogenesis of the mammalian urogenital system. Developmental Cell 9: 283–292.

Carroll TJ and Yu J (2012) The kidney and planar cell polarity. Current Topics in Developmental Biology 101: 185–212.

Cheng HT , Kim M , Valerius MT et al. (2007) Notch2, but not Notch1, is required for proximal fate acquisition in the mammalian nephron. Development 134: 801–811.

Costantini F and Kopan R (2010) Patterning a complex organ: branching morphogenesis and nephron segmentation in kidney development. Developmental Cell 18: 698–712.

Davies JA (2005) Mechanisms of Morphogenesis, 1st edn. London: Academic Press.

Davies JA and Garrod DR (1995) Induction of early stages of kidney tubule differentiation by lithium ions. Developmental Biology 167: 50–60.

Fujimura S , Jiang Q , Kobayashi C and Nishinakamura R (2010) Notch2 activation in the embryonic kidney depletes nephron progenitors. Journal of the American Society of Nephrology 21: 803–810.

Gersh I (1937) The correlation of structure and function in the developing mesonephros and metanephros. Contributions to Embryology 153: 35–58.

Gong KQ , Yallowitz AR , Sun H , Dressler GR and Wellik DM (2007) A Hox‐Eya‐Pax complex regulates early kidney developmental gene expression. Molecular and Cellular Biology 27: 7661–7668.

Gruenwald P (1942) Experimental on the distribution and activation of the nephrogenic potency in the embryonic mesenchyme. Physiological Zoology 15: 396–409.

James RG , Kamei CN , Wang Q , Jiang R and Schultheiss TM (2006) Odd‐skipped related 1 is required for development of the metanephric kidney and regulates formation and differentiation of kidney precursor cells. Development 133: 2995–3004.

Kitamoto Y , Tokunaga H and Tomita K (1997) Vascular endothelial growth factor is an essential molecule for mouse kidney development: glomerulogenesis and nephrogenesis. Journal of Clinical Investigation 99: 2351–2357.

Kobayashi A , Valerius MT , Mugford JW et al. (2008) Six2 defines and regulates a multipotent self‐renewing nephron progenitor population throughout mammalian kidney development. Cell Stem Cell 3: 169–181.

Kopan R , Cheng HT and Surendran K (2007) Molecular insights into segmentation along the proximal‐distal axis of the nephron. Journal of the American Society of Nephrology 18: 2014–2020.

Little MH , Brennan J , Georgas K et al. (2007) A high‐resolution anatomical ontology of the developing murine genitourinary tract. Gene Expression Patterns 7: 680–699.

Majumdar A , Vainio S , Kispert A , McMahon J and McMahon AP (2003) Wnt11 and Ret/Gdnf pathways cooperate in regulating ureteric branching during metanephric kidney development. Development 130: 3175–3185.

Meyer TN , Schwesinger C , Sampogna RV et al. (2006) Rho kinase acts at separate steps in ureteric bud and metanephric mesenchyme morphogenesis during kidney development. Differentiation 74: 638–647.

Michael L and Davies JA (2004) Pattern and regulation of cell proliferation during murine ureteric bud development. Journal of Anatomy 204: 241–255.

Michael L , Sweeney DE and Davies JA (2005) A role for microfilament‐based contraction in branching morphogenesis of the ureteric bud. Kidney International 68: 2010–2018.

Nakamura KT , Matherne GP , McWeeny OJ , Smith BA and Robillard JE (1987) Renal hemodynamics and functional changes during the transition from fetal to newborn life in sheep. Pediatric Research 21: 229–234.

Niimura F , Labosky PA , Kakuchi J et al. (1995) Gene targeting in mice reveals a requirement for angiotensin in the development and maintenance of kidney morphology and growth factor regulation. Journal of Clinical Investigation 96: 2947–2954.

Park JS , Ma W , O'Brien LL et al. (2012) Six2 and Wnt regulate self‐renewal and commitment of nephron progenitors through shared gene regulatory networks. Developmental Cell 23: 637–651.

Park JS , Valerius MT and McMahon AP (2007) Wnt/beta‐catenin signaling regulates nephron induction during mouse kidney development. Development 134: 2533–2539.

Rak‐Raszewska A , Wilm B , Edgar D et al. (2012) Development of embryonic stem cells in recombinant kidneys. Organogenesis 8: 1–6.

Sainio K , Suvanto P , Davies J et al. (1997) Glial‐cell‐line‐derived neurotrophic factor is required for bud initiation from ureteric epithelium. Development 124: 4077–4087.

Satlin LM , Woda CB and Schwartz GJ (2003) Development of function in the metanephric kidney. In: Vize P , Woolf AS and Bard JBL (eds) The Kidney, London: Academic Press.

Schwartz GJ and Evan AP (1984) Development of solute transport in rabbit proximal tubule. III. Na‐K‐ATPase activity. American Journal of Physiology 1246: F845–F852.

Self M , Lagutin OV , Bowling B et al. (2006) Six2 is required for suppression of nephrogenesis and progenitor renewal in the developing kidney. EMBO Journal 25: 5214–5228.

Stark K , Vainio S , Vassileva G and McMahon AP (1994) Epithelial transformation of metanephric mesenchyme in the developing kidney regulated by Wnt‐4. Nature 372: 679–683.

Surendran K , Selassie M , Liapis H , Krigman H and Kopan R (2010) Reduced Notch signaling leads to renal cysts and papillary microadenomas. Journal of the American Society of Nephrology 21: 819–832.

Unbekandt M and Davies JA (2010) Dissociation of embryonic kidneys followed by reaggregation allows the formation of renal tissues. Kidney International 77: 407–416.

Watanabe T and Costantini F (2004) Real‐time analysis of ureteric bud branching morphogenesis in vitro . Developmental Biology 271: 98–108.

Woolf AS , Kolatsi‐Joannou M , Hardman P et al. (1995) Roles of hepatocyte growth factor/scatter factor and the met receptor in the early development of the metanephros. Journal of Cell Biology 128: 171–184.

Woolf AS and Loughna S (1998) Origin of glomerular capillaries: is the verdict in? Experimental Nephrology 6: 17–21.

Xinaris C , Benedetti V , Rizzo P et al. (2012) In vivo maturation of functional renal organoids formed from embryonic cell suspensions. Journal of the American Society of Nephrology 23: 1857–1868.

Yosypiv IV (2008) A new role for the renin‐angiotensin system in the development of the ureteric bud and renal collecting system. Keio Journal of Medicine 57: 184–189.

Yu CT , Tang K , Suh JM et al. (2012) COUP‐TFII is essential for metanephric mesenchyme formation and kidney precursor cell survival. Development 139: 2330–2339.

Yuan HT , Suri C , Landon DN , Yancopoulos GD and Woolf AS (2000) Angiopoietin‐2 is a site‐specific factor in differentiation of mouse renal vasculature. Journal of the American Society of Nephrology 11: 1055–1066.

Further Reading

Saxen L (1986) Organogenesis of the Kidney. Cambridge: Cambridge University Press.

Vize P , Woolf AS and Bard JBL (2003) The Kidney. London: Academic Press.

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Davies, Jamie(Sep 2013) Kidney Development. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0001152.pub3]