Towards a quantitative model of kidney morphogenesis

Kidney growth is dependent on functional interactions between mesenchymal nephron progenitors, the ureteric epithelium and surrounding stroma, which together make up the nephrogenic niche. Signalling between these populations regulates nephron progenitor maintenance, branching morphogenesis and nephron induction. Nephron endowment is sensitive to changes in the size of the nephron progenitor pool and to decreases in factors that promote branching morphogenesis. However, determining the morphogenic consequences of these disruptions in vivo has been challenging as quantitating kidney morphogenesis is hampered by the size, opacity and three-dimensional complexity of the tissue. The recent application of whole mount immunofluorescence and tissue clearing, coupled with multiscale imaging and quantitative analysis, has begun to give insights into the dynamics of kidney formation. This review focuses on how the quantitative nature of this approach has enabled mathematical modelling of cell cycle lengths, growth rates, cell number and branching rates and is advancing our understanding of kidney organogenesis. Summary at a Glance This solicited mini-review, which relates to the topic of a talk given at the Asia-Pacific Kidney Development Workshop in Queenstown, New Zealand (22-23 September 2014), discusses how advances in the imaging of embryonic kidneys are leading to the establishment of a quantitative model of kidney organogenesis that will predict collecting duct branching, growth and final nephron number.