title: A fate-mapping approach reveals the composite origin of the connecting tubule and alerts on "single-cell"-specific KO model of the distal nephron.
abstract: The distal nephron is a heterogeneous part of the nephron composed by six different cell types, forming the epithelium of the distal convoluted (DCT), connecting, and collecting duct. To dissect the function of these cells, knockout models specific for their unique cell marker have been created. However, since this part of the nephron develops at the border between the ureteric bud and the metanephric mesenchyme, the specificity of the single cell markers has been recently questioned. Here, by mapping the fate of the aquaporin 2 (AQP2) and Na+-Cl-cotransporter (NCC)-positive cells using transgenic mouse lines expressing the yellow fluorescent protein fluorescent marker, we showed that the origin of the distal nephron is extremely composite. Indeed, AQP2-expressing precursor results give rise not only to the principal cells, but also to some of the A- and B-type intercalated cells and even to cells of the DCT. On the other hand, some principal cells and B-type intercalated cells can develop from NCC-expressing precursors. In conclusion, these results demonstrate that the origin of different cell types in the distal nephron is not as clearly defined as originally thought. Importantly, they highlight the fact that knocking out a gene encoding for a selective functional marker in the adult does not guarantee cell specificity during the overall kidney development. Tools allowing not only cell-specific but also time-controlled recombination will be useful in this sense.
authors: Department of Cardio-Thoracic and Respiratory Science, Second University of Naples, Caserta, Italy; francesco.trepiccione@unina2.it.|INSERM U970, Paris Cardiovascular Research Center, Université Paris-Descartes, Paris, France.
authors: Francesco
authors: F
authors: Trepiccione
authors: INSERM U970, Paris Cardiovascular Research Center, Université Paris-Descartes, Paris, France.
authors: Christelle
authors: C
authors: Soukaseum
authors: Biogem, Istituto di Ricerche Genetiche Gaetano Salvatore, Ariano Irpino, Italy; and.
authors: Anna
authors: A
authors: Iervolino
authors: Department of Cardio-Thoracic and Respiratory Science, Second University of Naples, Caserta, Italy.|Biogem, Istituto di Ricerche Genetiche Gaetano Salvatore, Ariano Irpino, Italy; and.
authors: Federica
authors: F
authors: Petrillo
authors: Department of Cardio-Thoracic and Respiratory Science, Second University of Naples, Caserta, Italy.
authors: Miriam
authors: M
authors: Zacchia
authors: German Cancer Research Center, Division Molecular Biology of the Cell, Heidelberg, Germany.
authors: Gunther
authors: G
authors: Schutz
authors: INSERM U970, Paris Cardiovascular Research Center, Université Paris-Descartes, Paris, France.
authors: Dominique
authors: D
authors: Eladari
authors: Department of Cardio-Thoracic and Respiratory Science, Second University of Naples, Caserta, Italy.|Biogem, Istituto di Ricerche Genetiche Gaetano Salvatore, Ariano Irpino, Italy; and.
authors: Giovambattista
authors: G
authors: Capasso
authors: INSERM U970, Paris Cardiovascular Research Center, Université Paris-Descartes, Paris, France.
authors: Juliette
authors: J
authors: Hadchouel
mesh_terms: D000818:Animals; D051399:Aquaporin 2 / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D007686:Kidney Tubules, Distal / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009399:Nephrons / Q000378:metabolism*; D049992:Sodium Chloride Symporters / Q000378:metabolism
chemical_list: D051399:Aquaporin 2; D049992:Sodium Chloride Symporters
keywords: AQP2; NCC; connecting tubule; distal nephron; fate mapping