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, 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.
Barasch
J
J
Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA. jmb4@columbia.edu
Yang
J
J
Ware
C B
CB
Taga
T
T
Yoshida
K
K
Erdjument-Bromage
H
H
Tempst
P
P
Parravicini
E
E
Malach
S
S
Aranoff
T
T
Oliver
J A
JA
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D050822:Cytokine Receptor gp130; D004268:DNA-Binding Proteins / Q000378:metabolism; D004627:Embryonic Induction; D004848:Epithelium / Q000196:embryology*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006131:Growth Inhibitors / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D015850:Interleukin-6 / Q000378:metabolism; D007684:Kidney Tubules / Q000196:embryology; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008024:Ligands; D008222:Lymphokines / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D008648:Mesoderm / Q000502:physiology*; D051379:Mice; D009399:Nephrons / Q000196:embryology*; D051762:PAX2 Transcription Factor; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051381:Rats; D018121:Receptors, Cytokine / Q000378:metabolism; D053606:Receptors, OSM-LIF; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014513:Ureter / Q000166:cytology / Q000196:embryology*; D051153:Wnt Proteins; D060528:Wnt4 Protein
D015703:Antigens, CD; D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; C494200:Il6st protein, mouse; C494201:Il6st protein, rat; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; C507838:Lif protein, mouse; C507841:Lifr protein, mouse; C507842:Lifr protein, rat; D008024:Ligands; D008222:Lymphokines; D008562:Membrane Glycoproteins; D051762:PAX2 Transcription Factor; C497319:Pax2 protein, mouse; D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine; D053606:Receptors, OSM-LIF; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C494088:Stat3 protein, rat; D015534:Trans-Activators; D014157:Transcription Factors; D051153:Wnt Proteins; D060528:Wnt4 Protein; C555582:Wnt4 protein, mouse; C555583:Wnt4 protein, rat; D016222:Fibroblast Growth Factor 2; D050822:Cytokine Receptor gp130