Kidney Development

Abstract

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 – http://www.gudmap.org

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.

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Further Reading

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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. http://www.els.net [doi: 10.1002/9780470015902.a0001152.pub3]