The mouse kidney is an excellent model for studying biological process central to proper embryonic development including stem cell maintenance and differentiation, reciprocal tissue interactions, branching morphogenesis and tube formation, and cell-fate specification. These processes are required to make nephrons, the filtering units of the mammalian kidney. For this, mesenchymal stem cells exit a niche and undergo a stepwise process of epithelialization, morphogenesis, and fate specification that results in the production of over 20 specialized cell types central to the function of the kidney. The kidney group in the Kopan Lab is interested in the molecular mechanisms that regulate these processes, and have identified critical roles for Notch and FGF signaling during the early stages of nephron formation.
Liu, Z., Chen, S., Boyle, S., Ilagan, M.X., Zhu, Y., Zhang, A., and Kopan, R. The Extracellular Domain of Notch2 Increases its Cell surface Abundance and Ligand Responsiveness During Kidney. Dev Cell. 2013 Jun 24;25(6):585-98.
Barak, H. et al. FGF9 and FGF20 maintain the stemness of nephron progenitors in mice and man. Developmental Cell. 2012 Jun 12;22(6):1191-207.
Surendran, K. et al. Chromatin-based Mechanisms of Renal Epithelial Differentiation. J Am Soc Nephrol. 2011 Jul;22(7):1208-12.
Surendran, K. et al. Reduced Notch signaling leads to renal cysts and papillary microadenomas. J Am Soc Nephrol. 2010 May;21(5):819-32.
Surendran, K. et al. The contribution of Notch1 to nephron segmentation in the developing kidney is revealed in a sensitized Notch2 background and can be augmented by reducing Mint dosage. Dev Biol. 2010 Jan 15;337(2):386-95.
Kopan, R. et al. Molecular Insights into Segmentation along the Proximal-Distal Axis of the Nephron. J Am Soc Nephrol. 2007 Jul;18(7):2014-20.
Cheng, H. T. et al. Notch2, but not Notch1, is required for proximal fate acquisition in the mammalian nephron. Development. 2007 Feb;134(4):801-11.
Cheng, H. T. et al. The role of Notch signaling in specification of podocyte and proximal tubules within the developing mouse kidney. Kidney Int. 2005 Nov;68(5):1951-2.
Cheng, H. et al. g-Secretase Activity is Dispensable for the Mesenchyme-to-Epithelium Transition but Required for Proximal Tubule Formation in Developing Mouse Kidney. Development. 2003 Oct;130(20):5031-42.