Global quantification of tissue dynamics in the developing mouse kidney.
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.
Department of Biochemistry and Molecular Biology, Monash University, Clayton VIC 3800, Australia.
Kieran M
KM
Short
Division of Molecular Genetics and Development, Institute for Molecular Bioscience, The University of Queensland, Brisbane QLD 4072, Australia.
Alexander N
AN
Combes
Division of Genomics & Computational Biology and Division of Molecular Cell Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane QLD 4072, Australia.
James
J
Lefevre
Division of Molecular Genetics and Development, Institute for Molecular Bioscience, The University of Queensland, Brisbane QLD 4072, Australia.
Adler L
AL
Ju
Division of Molecular Genetics and Development, Institute for Molecular Bioscience, The University of Queensland, Brisbane QLD 4072, Australia.
Kylie M
KM
Georgas
Division of Genomics & Computational Biology and Division of Molecular Cell Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane QLD 4072, Australia.
Timothy
T
Lamberton
Division of Genomics & Computational Biology and Division of Molecular Cell Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane QLD 4072, Australia.
Oliver
O
Cairncross
Division of Molecular Genetics and Development, Institute for Molecular Bioscience, The University of Queensland, Brisbane QLD 4072, Australia.
Bree A
BA
Rumballe
Department of Stem Cell Biology and Regenerative Medicine, Broad-CIRM Center for Regenerative Medicine and Stem Cell Research, University of Southern California Keck School of Medicine, Los Angeles, CA 90089, USA.
Andrew P
AP
McMahon
Division of Genomics & Computational Biology and Division of Molecular Cell Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane QLD 4072, Australia.
Nicholas A
NA
Hamilton
Department of Biochemistry and Molecular Biology, Monash University, Clayton VIC 3800, Australia; Department of Anatomy and Developmental Biology, Monash University, Clayton VIC 3800, Australia. Electronic address: ian.smyth@monash.edu.
Ian M
IM
Smyth
Division of Molecular Genetics and Development, Institute for Molecular Bioscience, The University of Queensland, Brisbane QLD 4072, Australia. Electronic address: m.little@imb.uq.edu.au.
Melissa H
MH
Little
D000818:Animals; D002452:Cell Count; D053595:Embryonic Stem Cells / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D007668:Kidney / Q000166:cytology / Q000196:embryology* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009399:Nephrons / Q000166:cytology / Q000196:embryology* / Q000502:physiology; D010641:Phenotype; D011247:Pregnancy; D014513:Ureter / Q000166:cytology / Q000196:embryology* / Q000502:physiology; D019459:Urothelium / Q000166:cytology / Q000196:embryology* / Q000502:physiology