Recombination signal sequence-binding protein Jkappa alters mesodermal cell fate decisions by suppressing cardiomyogenesis.
The transcription factor recombination signal sequence-binding protein Jkappa (RBP-J) is a key downstream element in the signaling pathway of all four mammalian Notch receptors that are critically involved in the control of embryonic and adult development. RBP-J-deficient mice display complex defects and die around day 9.5 postcoitum. Here, we investigate the function of RBP-J in the development of mesodermal cell lineages by using the OP9 stroma coculture system. RBP-J-deficient embryonic stem (ES) cells gave rise to cardiomyocytes, endothelial cells, and primitive and definitive hematopoietic cells. Thus, RBP-J-mediated signals are not required for generation of these cell types. However, when compared with parental RBP-J-expressing ES cells, cardiomyogenesis derived from RBP-J-deficient ES cells was increased. Repression over the cardiogenic pathway was restored by expressing RBP-J in RBP-J-deficient ES cells. Our data indicate that Notch signaling via RBP-J plays an important role for the correct specification of myocardial cell fates.
Schroeder
Timm
T
GSF-National Research Center for Environment and Health, Institute of Clinical Molecular Biology and Tumor Genetics, Marchioninistrasse 25, 81377 Munich, Germany.
Fraser
Stuart T
ST
Ogawa
Minetaro
M
Nishikawa
Satomi
S
Oka
Chio
C
Bornkamm
Georg W
GW
Nishikawa
Shin-Ichi
S
Honjo
Tasuku
T
Just
Ursula
U
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005314:Embryonic and Fetal Development; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology*; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D008648:Mesoderm / Q000166:cytology* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology
D004268:DNA-Binding Proteins; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D009687:Nuclear Proteins; C497571:Rbpj protein, mouse; D012097:Repressor Proteins