Msx2-interacting nuclear target protein (Mint) deficiency reveals negative regulation of early thymocyte differentiation by Notch/RBP-J signaling.
Notch/RBP-J signaling is required for generation of early T progenitors (ETP) and promotion of double-negative (DN) 4 cells from DN3 cells in thymocyte differentiation. However, whether Notch affects other steps during thymocyte differentiation remains unknown. Msx2-interacting nuclear target protein (Mint) is an endogenous inhibitor of Notch regulation. Concordantly, by ex vivo analyses of embryonic thymi and in vitro differentiation studies of fetal liver progenitors, we find that Mint deficiency enhances generation of ETP and DN4 cells. Unexpectedly, however, Mint deficiency impairs differentiation of ETP into DN2 cells, suggesting that Notch/RBP-J signaling negatively regulates DN1-DN2 transition.
Tsuji
Masayuki
M
Department of Immunology, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan.
Shinkura
Reiko
R
Kuroda
Kazuki
K
Yabe
Daisuke
D
Honjo
Tasuku
T
D000818:Animals; D002454:Cell Differentiation; D003433:Crosses, Genetic; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D009687:Nuclear Proteins / Q000235:genetics* / Q000502:physiology*; D016601:RNA-Binding Proteins; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology* / Q000378:metabolism
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; C484553:Rbpsuhl protein, mouse; D051880:Receptors, Notch; C121253:Spen protein, mouse