title: The PI3K pathway balances self-renewal and differentiation of nephron progenitor cells through β-catenin signaling.
abstract: Nephron progenitor cells differentiate to form nephrons during embryonic kidney development. In contrast, self-renewal maintains progenitor numbers and premature depletion leads to impaired kidney function. Here we analyze the PI3K pathway as a point of convergence for the multiple pathways that are known to control self-renewal in the kidney. We demonstrate that a reduction in PI3K signaling triggers premature differentiation of the progenitors and activates a differentiation program that precedes the mesenchymal-to-epithelial transition through ectopic activation of the β-catenin pathway. Therefore, the combined output of PI3K and other pathways fine-tunes the balance between self-renewal and differentiation in nephron progenitors.
authors.affiliation: The Roslin Institute, University of Edinburgh, Easter Bush Campus, Midlothian EH25 9RG, UK; Edinburgh Cancer Research Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XR, UK. Electronic address: nils.lindstrom@roslin.ed.ac.uk.
authors.forename: Nils Olof
authors.initials: NO
authors.lastname: Lindström
authors.affiliation: Edinburgh Cancer Research Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XR, UK.
authors.forename: Neil Oliver
authors.initials: NO
authors.lastname: Carragher
authors.affiliation: The Roslin Institute, University of Edinburgh, Easter Bush Campus, Midlothian EH25 9RG, UK; MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK. Electronic address: peter.hohenstein@roslin.ed.ac.uk.
authors.forename: Peter
authors.initials: P
authors.lastname: Hohenstein
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D000066673:Cell Self Renewal; D005260:Female; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009399:Nephrons / Q000166:cytology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D051176:beta Catenin