AML1/Runx1 rescues Notch1-null mutation-induced deficiency of para-aortic splanchnopleural hematopoiesis.
The Notch1-RBP-Jkappa and the transcription factor Runx1 pathways have been independently shown to be indispensable for the establishment of definitive hematopoiesis. Importantly, expression of Runx1 is down-regulated in the para-aortic splanchnopleural (P-Sp) region of Notch1- and Rbpsuh-null mice. Here we demonstrate that Notch1 up-regulates Runx1 expression and that the defective hematopoietic potential of Notch1-null P-Sp cells is successfully rescued in the OP9 culture system by retroviral transfer of Runx1. We also show that Hes1, a known effector of Notch signaling, potentiates Runx1-mediated transactivation. Together with the recent findings in zebrafish, Runx1 is postulated to be a cardinal down-stream mediator of Notch signaling in hematopoietic development throughout vertebrates. Our findings also suggest that Notch signaling may modulate both expression and transcriptional activity of Runx1.
Nakagawa
Masahiro
M
Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Japan.
Ichikawa
Motoshi
M
Kumano
Keiki
K
Goyama
Susumu
S
Kawazu
Masahito
M
Asai
Takashi
T
Ogawa
Seishi
S
Kurokawa
Mineo
M
Chiba
Shigeru
S
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D050676:Core Binding Factor Alpha 2 Subunit / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D051881:Receptor, Notch1 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D014161:Transduction, Genetic; D014781:Viscera / Q000166:cytology
D050676:Core Binding Factor Alpha 2 Subunit; C497762:Notch1 protein, mouse; C493728:RUNX1 protein, human; D051881:Receptor, Notch1