title: AML1/Runx1 rescues Notch1-null mutation-induced deficiency of para-aortic splanchnopleural hematopoiesis.
abstract: 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.
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Motoshi
authors.initials: M
authors.lastname: Ichikawa
authors.forename: Keiki
authors.initials: K
authors.lastname: Kumano
authors.forename: Susumu
authors.initials: S
authors.lastname: Goyama
authors.forename: Masahito
authors.initials: M
authors.lastname: Kawazu
authors.forename: Takashi
authors.initials: T
authors.lastname: Asai
authors.forename: Seishi
authors.initials: S
authors.lastname: Ogawa
authors.forename: Mineo
authors.initials: M
authors.lastname: Kurokawa
authors.forename: Shigeru
authors.initials: S
authors.lastname: Chiba
mesh_terms: 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
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; C497762:Notch1 protein, mouse; C493728:RUNX1 protein, human; D051881:Receptor, Notch1