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WT1 controls antagonistic FGF and BMP-pSMAD pathways in early renal progenitors

Item Type:Article
Title:WT1 controls antagonistic FGF and BMP-pSMAD pathways in early renal progenitors
Creators Name:Motamedi, F.J. and Badro, D.A. and Clarkson, M. and Rita Lecca, M. and Bradford, S.T. and Buske, F.A. and Saar, K. and Huebner, N. and Braendli, A.W. and Schedl, A.
Abstract:Kidney organogenesis requires the tight control of proliferation, differentiation and apoptosis of renal progenitor cells. How the balance between these cellular decisions is achieved remains elusive. The Wilms' tumour suppressor Wt1 is required for progenitor survival, but the molecular cause for renal agenesis in mutants is poorly understood. Here we demonstrate that lack of Wt1 abolishes fibroblast growth factor (FGF) and induces BMP/pSMAD signalling within the metanephric mesenchyme. Addition of recombinant FGFs or inhibition of pSMAD signalling rescues progenitor cell apoptosis induced by the loss of Wt1. We further show that recombinant BMP4, but not BMP7, induces an apoptotic response within the early kidney that can be suppressed by simultaneous addition of FGFs. These data reveal a hitherto unknown sensitivity of early renal progenitors to pSMAD signalling, establishes FGF and pSMAD signalling as antagonistic forces in early kidney development and places WT1 as a key regulator of pro-survival FGF signalling pathway genes.
Keywords:Bone Morphogenetic Proteins, Cell Differentiation, Computational Biology, Developmental Gene Expression Regulation, Fibroblast Growth Factors, Fluorescent Antibody Technique, In Situ Hybridization, In Situ Nick-End Labeling, Mutant Strains Mice, Organ Culture Techniques, Repressor Proteins, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Stem Cells, Animals, Mice
Source:Nature Communications
ISSN:2041-1723
Publisher:Nature Publishing Group (U.K.)
Volume:5
Page Range:4444
Date:17 July 2014
Official Publication:https://doi.org/10.1038/ncomms5444
PubMed:View item in PubMed

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