C-myc as a modulator of renal stem/progenitor cell population.
The role of c-myc has been well-studied in gene regulation and oncogenesis but remains elusive in murine development from midgestation. We determined c-myc function during kidney development, organogenesis, and homeostasis by conditional loss of c-myc induced at two distinct phases of nephrogenesis, embryonic day (e) 11.5 and e17.5. Deletion of c-myc in early metanephric mesenchyme (e11.5) led to renal hypoplasia from e15.5 to e17.5 that was sustained until adulthood (range, 20-25%) and, hence, reproduced the human pathologic condition of renal hypoplasia. This phenotype resulted from depletion of c-myc-positive cells in cap mesenchyme, causing a approximately 35% marked decrease of Six2- and Cited1-stem/progenitor population and of proliferation that likely impaired self-renewal. By contrast, c-myc loss from e17.5 onward had no impact on late renal differentiation/maturation and/or homeostasis, providing evidence that c-myc is dispensable during these phases. This study identified c-myc as a modulator of renal organogenesis through regulation of stem/progenitor cell population.
Couillard
Martin
M
Institut de recherches cliniques de Montreal, Molecular Genetics and Development, Faculte de medecine de l'Universite de Montreal, Montreal, Quebec, Canada.
Trudel
Marie
M
D000818:Animals; D051017:Apoptosis Regulatory Proteins; D002454:Cell Differentiation / Q000502:physiology; D018398:Homeodomain Proteins / Q000378:metabolism; D006706:Homeostasis; D007668:Kidney / Q000002:abnormalities / Q000196:embryology / Q000378:metabolism*; D008648:Mesoderm / Q000196:embryology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000378:metabolism; D038081:Organogenesis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C102208:Cited1 protein, mouse; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; C497420:Six2 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors