AML1/Runx1 rescues Notch1-null mutation-induced deficiency of para-aortic splanchnopleural hematopoiesis

M Nakagawa, M Ichikawa, K Kumano, S Goyama… - Blood, 2006 - ashpublications.org
M Nakagawa, M Ichikawa, K Kumano, S Goyama, M Kawazu, T Asai, S Ogawa, M Kurokawa…
Blood, 2006ashpublications.org
Abstract The Notch1-RBP-Jκ 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 …
Abstract
The Notch1-RBP-Jκ 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.
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