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First published online 17 September 2008
doi: 10.1242/dev.025916

Development 135, 3447-3458 (2008)
Published by The Company of Biologists 2008
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Numb mediates the interaction between Wnt and Notch to modulate primitive erythropoietic specification from the hemangioblast

Xin Cheng1, Tara L. Huber2, Vincent C. Chen1, Paul Gadue1 and Gordon M. Keller3,*

1 Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
2 Stem Cell and Developmental Biology Department, Genome Institute of Singapore, 138672 Singapore.
3 McEwen Centre for Regenerative Medicine, University Health Network, Toronto, Ontario M5G 1L7, Canada.

* Author for correspondence (e-mail: gkeller{at}uhnresearch.ca)

Accepted 1 September 2008

During embryonic development, the establishment of the primitive erythroid lineage in the yolk sac is a temporally and spatially restricted program that defines the onset of hematopoiesis. In this report, we have used the embryonic stem cell differentiation system to investigate the regulation of primitive erythroid development at the level of the hemangioblast. We show that the combination of Wnt signaling with inhibition of the Notch pathway is required for the development of this lineage. Inhibition of Notch signaling at this stage appears to be mediated by the transient expression of Numb in the hemangioblast-derived blast cell colonies. Activation of the Notch pathway was found to inhibit primitive erythropoiesis efficiently through the upregulation of inhibitors of the Wnt pathway. Together, these findings demonstrate that specification of the primitive erythroid lineage is controlled, in part, by the coordinated interaction of the Wnt and Notch pathways, and position Numb as a key mediator of this process.

Key words: Notch signaling, Numb, Wnt signaling, Hemangioblast, Primitive erythropoiesis


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