Evi1 regulates Notch activation to induce zebrafish hematopoietic stem cell emergence

Konantz, Martina and Alghisi, Elisa and Müller, Joëlle S. and Lenard, Anna and Esain, Virginie and Carroll, Kelli J. and Kanz, Lothar and North, Trista E. and Lengerke, Claudia. (2016) Evi1 regulates Notch activation to induce zebrafish hematopoietic stem cell emergence. The EMBO Journal, 35 (21). pp. 2315-2331.

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Official URL: https://edoc.unibas.ch/62306/

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During development, hematopoietic stem cells (HSCs) emerge from aortic endothelial cells (ECs) through an intermediate stage called hemogenic endothelium by a process known as endothelial-to-hematopoietic transition (EHT). While Notch signaling, including its upstream regulator Vegf, is known to regulate this process, the precise molecular control and temporal specificity of Notch activity remain unclear. Here, we identify the zebrafish transcriptional regulator evi1 as critically required for Notch-mediated EHT In vivo live imaging studies indicate that evi1 suppression impairs EC progression to hematopoietic fate and therefore HSC emergence. evi1 is expressed in ECs and induces these effects cell autonomously by activating Notch via pAKT Global or endothelial-specific induction of notch, vegf, or pAKT can restore endothelial Notch and HSC formations in evi1 morphants. Significantly, evi1 overexpression induces Notch independently of Vegf and rescues HSC numbers in embryos treated with a Vegf inhibitor. In sum, our results unravel evi1-pAKT as a novel molecular pathway that, in conjunction with the shh-vegf axis, is essential for activation of Notch signaling in VDA endothelial cells and their subsequent conversion to HSCs.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Stem Cells and Hematopoiesis (Lengerke)
UniBasel Contributors:Lengerke, Claudia
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:EMBO Press
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:11 Sep 2018 18:00
Deposited On:26 May 2018 16:40

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