Global Quantification of Tissue Dynamics in the Developing Mouse Kidney

• Published in: Developmental cell Vol. 29; no. 2; pp. 188 - 202
• Main Authors: Short, Kieran M., Combes, Alexander N., Lefevre, James, Ju, Adler L., Georgas, Kylie M., Lamberton, Timothy, Cairncross, Oliver, Rumballe, Bree A., McMahon, Andrew P., Hamilton, Nicholas A., Smyth, Ian M., Little, Melissa H.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 28.04.2014
• Subjects: Animals; Cell Count; Embryonic Stem Cells - physiology; Female; Gene Expression Regulation, Developmental; Kidney - cytology; Kidney - embryology; Kidney - physiology; Male; Mice; Mice, Inbred C57BL; Mutation; Nephrons - cytology; Nephrons - embryology; Nephrons - physiology; Phenotype; Pregnancy; Ureter - cytology; Ureter - embryology; Ureter - physiology; Urothelium - cytology; Urothelium - embryology; Urothelium - physiology
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2014.02.017

Although kidneys of equal size can vary 10-fold in nephron number at birth, discovering what regulates such variation has been hampered by a lack of quantitative parameters defining kidney development. Here we report a comprehensive, quantitative, multiscale analysis of mammalian kidney development in which we measure changes in cell number, compartment volumes, and cellular dynamics across the entirety of organogenesis, focusing on two key nephrogenic progenitor populations: the ureteric epithelium and the cap mesenchyme. In doing so, we describe a discontinuous developmental program governed by dynamic changes in interactions between these key cellular populations occurring within a previously unappreciated structurally stereotypic organ architecture. We also illustrate the application of this approach to the detection of a subtle mutant phenotype. This baseline program of kidney morphogenesis provides a framework for assessing genetic and environmental developmental perturbation and will serve as a gold standard for the analysis of other organs. •A comprehensive temporospatial and multiscale profile of normal kidney development•Analysis of structural stereotypy and branch form across development•Dynamic changes in the cap and tip progenitor cell niches over time•Application of the approach to identify a subtle mutant phenotype Short et al. describe a comprehensive, quantitative analysis of shape, cell number, and proliferation rate for key progenitor populations across mammalian kidney development. This reveals a morphogenetic program with structural stereotypy, asynchronous branching, substantial remodeling, and discontinuous nephron induction, elucidating how variation in size and nephron number may arise.