Submitted April 25, 2006
Accepted July 3, 2006
AML1/Runx1 rescues Notch1-Null mutation-induced deficiency
of para-aortic splanchnopleural hematopoiesis
Masahiro Nakagawa, Motoshi Ichikawa, Keiki Kumano, Susumu Goyama, Masahito Kawazu, Takashi Asai, Seishi Ogawa, Mineo Kurokawa, and Shigeru Chiba*
Departments of Hematology and Oncology, University of Tokyo, Japan
Departments of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Japan
Departments of Hematology and Oncology, University of Tokyo; University of Tokyo Hospital, Japan
* Corresponding author; email: schiba-tky{at}umin.ac.jp.
The Notch1-RBP-J
and the transcription factor
Runx1 pathways have been independently shown to be
indispensable for 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 downstream 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.
