Mesenchymal to Epithelial Conversion in Rat Metanephros Is Induced by LIF

• Published in: Cell 1999-11, Vol.99 (4), p.377-386
• Main Authors: Barasch, Jonathan, Yang, Jun, Ware, Carol B, Taga, Tetsuya, Yoshida, Kanji, Erdjument-Bromage, Hediye, Tempst, Paul, Parravicini, Elvira, Malach, Stephen, Aranoff, Tsvi, Oliver, Juan A
• Format: Article
• Language: English
• Subjects: Animals; Antigens, CD - metabolism; Cytokine Receptor gp130; DNA-Binding Proteins - metabolism; Embryonic Induction; Epithelium - embryology; Fibroblast Growth Factor 2 - metabolism; Growth Inhibitors - genetics; Growth Inhibitors - isolation & purification; Growth Inhibitors - physiology; Interleukin-6 - metabolism; Kidney Tubules - embryology; Leukemia Inhibitory Factor; Leukemia Inhibitory Factor Receptor alpha Subunit; Ligands; Lymphokines - genetics; Lymphokines - isolation & purification; Lymphokines - physiology; Membrane Glycoproteins - metabolism; Mesoderm - physiology; Mice; Nephrons - embryology; Pax2 gene; PAX2 Transcription Factor; Proto-Oncogene Proteins - metabolism; Rats; Receptors, Cytokine - metabolism; Receptors, OSM-LIF; Recombinant Proteins - metabolism; Recombinant Proteins - pharmacology; STAT3 Transcription Factor; Trans-Activators - metabolism; Transcription Factors - metabolism; Ureter - cytology; Ureter - embryology; Wnt Proteins; Wnt-4 gene; Wnt4 Protein
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/S0092-8674(00)81524-X

Inductive signals cause conversion of mesenchyme into epithelia during the formation of many organs. Yet a century of study has not revealed the inducing molecules. Using a standard model of induction, we found that ureteric bud cells secrete factors that convert kidney mesenchyme to epithelia that, remarkably, then form nephrons. Purification and sequencing of one such factor identified it as leukemia inhibitory factor (LIF). LIF acted on epithelial precursors that we identified by the expression of Pax2 and Wnt4. Other IL-6 type cytokines acted like LIF, and deletion of their shared receptor reduced nephron development. In situ, the ureteric bud expressed LIF, and metanephric mesenchyme expressed its receptors. The data suggest that IL-6 cytokines are candidate regulators of mesenchymal to epithelial conversion during kidney development.