Cell cycle arrest and apoptosis induced by Notch1 in B cells.
Notch receptors play various roles for cell fate decisions in developing organs, although their functions at the cell level are poorly understood. Recently, we found that Notch1 and its ligand are each expressed in juxtaposed cell compartments in the follicles of the bursa of Fabricius, the central organ for chicken B cell development. To examine the function of Notch1 in B cells, a constitutively active form of chicken Notch1 was expressed in a chicken B cell line, DT40, by a Cre/loxP-mediated inducible expression system. Remarkably, the active Notch1 caused growth suppression of the cells, accompanied by a cell cycle inhibition at the G(1) phase and apoptosis. The expression of Hairy1, a gene product up-regulated by the Notch1 signaling, also induced the apoptosis, but no cell cycle inhibition. Thus, Notch1 signaling induces apoptosis of the B cells through Hairy1, and the G(1) cell cycle arrest through other pathways. This novel function of Notch1 may account for the recent observations indicating the selective inhibition of early B cell development in mice by Notch1.
Morimura
T
T
Division of Molecular Biology, Research Institute for Biological Sciences, Science University of Tokyo, 2669 Yamazaki, Noda City, Chiba 278-0022, Japan.
Goitsuka
R
R
Zhang
Y
Y
Saito
I
I
Reth
M
M
Kitamura
D
D
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D030161:Avian Proteins; D001402:B-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D051792:Basic Helix-Loop-Helix Proteins; D001683:Biological Clocks; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002645:Chickens; D016193:G1 Phase / Q000187:drug effects; D008565:Membrane Proteins / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D009024:Morphogenesis; D011506:Proteins / Q000494:pharmacology; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D014157:Transcription Factors
D030161:Avian Proteins; D051792:Basic Helix-Loop-Helix Proteins; D008565:Membrane Proteins; D011506:Proteins; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D014157:Transcription Factors; C497762:Notch1 protein, mouse; C109424:hairy1 protein, Gallus gallus