Nephron progenitor cells: shifting the balance of self-renewal and differentiation.
Within the developing mammalian kidney, several populations of progenitors form the discrete cellular components of the final organ. Fate mapping experiments revealed the cap mesenchyme (CM) to be the progenitor population for all nephron epithelial cells, whereas the neighboring stromal mesenchyme gives rise to mesangial, pericytic, renin-producing and interstitial cells. The collecting ducts are derived from a population of progenitors at the ureteric bud (UB) tip and a proportion of the endothelium is also derived from a dedicated mesenchymal progenitor. The stroma, CM, and UB interact to create spatially defined niches at the periphery of the developing organ. While the UB tip population persist, the CM represents a transient progenitor population that is exhausted to set the final organ size. The timing of CM exhaustion, and hence the final organ structure, is sensitive to disruptions such as premature birth. Here we will discuss our current understanding of the molecular processes allowing these populations to balance cell survival, self-renewal, support of branching, and maintain capacity to commit to differentiation.
Department of Developmental Biology, Washington University, St. Louis, Missouri, USA; Division of Developmental Biology, Department of Pediatrics, Cincinnati Children's Hospital, Cincinnati, Ohio, USA. Electronic address: raphael.kopan@cchmc.org.
Raphael
R
Kopan
Department of Developmental Biology, Washington University, St. Louis, Missouri, USA.
Shuang
S
Chen
Department of Developmental Biology, Washington University, St. Louis, Missouri, USA; Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Queensland, Australia. Electronic address: m.little@imb.uq.edu.au.
Melissa
M
Little
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D060833:Cellular Microenvironment / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D051379:Mice; D009399:Nephrons / Q000166:cytology* / Q000196:embryology; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology*; D014566:Urogenital System / Q000196:embryology*
Branching; Cap mesenchyme; Metanephros; Six2; β-Catenin