Mesenchymal to Epithelial Conversion in Rat Metanephros Is Induced by LIF

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,...

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Bibliographic Details
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
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Summary: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.
ISSN:0092-8674
1097-4172
DOI:10.1016/S0092-8674(00)81524-X