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

First Author  Nakagawa M Year  2006
Journal  Blood Volume  108
Issue  10 Pages  3329-34
PubMed ID  16888092 Mgi Jnum  J:140445
Mgi Id  MGI:3813789 Doi  10.1182/blood-2006-04-019570
Citation  Nakagawa M, et al. (2006) AML1/Runx1 rescues Notch1-null mutation-induced deficiency of para-aortic splanchnopleural hematopoiesis. Blood 108(10):3329-34
abstractText  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.
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