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The contribution of branching morphogenesis to kidney development and disease

Nature Reviews Nephrology volume 12, pages 754–767 (2016)Cite this article

Subjects

Key Points

  • The basic architecture of the kidney is established during early embryonic development through iterative branching of the ureteric bud

  • Epithelial–mesenchymal cell interactions at the termini of the branching epithelium determine when and how many nephrons are generated

  • Genetic and/or environmental perturbations during kidney development can alter the developmental processes that direct branching and nephron formation and could, hence, underlie congenital and acquired nephron deficits

  • Nephron number in humans is determined at fetal stages and is emerging as a critical factor that influences adult health

Abstract

The mammalian kidney develops from a simple epithelial bud to an arborized network of tubules, which are fated to form the ureter, renal pelvis and collecting ducts. This process of ductal elaboration is achieved through an ancient developmental mechanism known as branching morphogenesis that is widely employed in glandular organs, the vasculature and lungs. It breaks up large solid tissues facilitating secretion, excretion and gas exchange, depending on the tissue. In the kidney, growth of the ureteric bud is driven by interactions between progenitor cells in the tips of the epithelial tree and their mesenchymal 'caps'. The cells of the cap mesenchyme give rise to nephrons; therefore, the interaction between these two cell populations is likely to be a critical driver of nephron number, which is determined during gestation. These cellular interactions are potentially affected by genetic mutations (congenital kidney diseases) and by changes in the fetal environment. Understanding the aetiology of congenital and acquired kidney diseases therefore requires a full appreciation of the processes involved in establishing the cellular architecture of the kidney and of the factors that affect the commitment of progenitor cells to form nephrons.

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Figure 1: Overview of mouse kidney development.
Figure 2: Features of branching morphogenesis.
Figure 3: Molecular determinants or ureteric bud formation.
Figure 4: Spatial features of branching morphogenesis.
Figure 5: Differences in kidney morphology across species.

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Acknowledgements

We acknowledge Dr Nicholas Hamilton and Dr James Lefevre from the University of Queensland for generating Figure 4.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Monash University, Wellington Rd, Clayton, 3800, Melbourne, Australia

    Kieran M. Short & Ian M. Smyth

  2. Monash Biomedicine Discovery Institute, 23 Innovation Walk, Monash University, Wellington Road, Clayton, 3800, Victoria, Australia

    Kieran M. Short & Ian M. Smyth

  3. Department of Anatomy and Developmental Biology, Monash University, 19 Innovation Walk, Clayton, 3800, Victoria, Australia

    Ian M. Smyth

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Morphometric analysis of branching morphogenesis during development (MP4 11012 kb)

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Short, K., Smyth, I. The contribution of branching morphogenesis to kidney development and disease. Nat Rev Nephrol 12, 754–767 (2016). https://doi.org/10.1038/nrneph.2016.157

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