Journal article
Haploinsufficiency for the Six2 gene increases nephron progenitor proliferation promoting branching and nephron number
AN Combes, S Wilson, B Phipson, BB Binnie, A Ju, KT Lawlor, C Cebrian, SL Walton, IM Smyth, KM Moritz, R Kopan, A Oshlack, MH Little
Kidney International | ELSEVIER SCIENCE INC | Published : 2018
Abstract
The regulation of final nephron number in the kidney is poorly understood. Cessation of nephron formation occurs when the self-renewing nephron progenitor population commits to differentiation. Transcription factors within this progenitor population, such as SIX2, are assumed to control expression of genes promoting self-renewal such that homozygous Six2 deletion results in premature commitment and an early halt to kidney development. In contrast, Six2 heterozygotes were assumed to be unaffected. Using quantitative morphometry, we found a paradoxical 18% increase in ureteric branching and final nephron number in Six2 heterozygotes, despite evidence for reduced levels of SIX2 protein and tran..
View full abstractGrants
Awarded by National Institute of Diabetes and Digestive and Kidney Diseases
Funding Acknowledgements
This work was supported by the Australian Research Council (DE150100652), the National Health and Medical Research Council of Australia (APP1002748, APP1063696), the Human Frontiers in Science Program (RGP0039/2011). Microscopy was performed at the ACRF/IMB Cancer Biology Imaging Facility at Monash University and the Murdoch Children's Research Institute. ANC holds a Discovery Early Career Researcher Award from the Australian Research Council. MHL is a Senior Principal Research Fellow of the NHMRC. We thank the IMB Sequencing Facility for NGS services, David Ornitz for the Fgf20 mice, Kieran Short, Lynelle Jones, Shireen Lamande, Chantal Coles, and Peter Houweling for technical assistance. MCRI is supported by the Victorian Government's Operational Infrastructure Support Program.