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XB-ART-46900
Dev Cell January 28, 2013; 24 (2): 144-58.

Uncoupling VEGFA functions in arteriogenesis and hematopoietic stem cell specification.

Leung A , Ciau-Uitz A , Pinheiro P , Monteiro R , Zuo J , Vyas P , Patient R , Porcher C .


Abstract
VEGFA signaling is critical for endothelial and hematopoietic stem cell (HSC) specification. However, blood defects resulting from perturbation of the VEGFA pathway are always accompanied by impaired vascular/arterial development. Because HSCs derive from arterial cells, it is unclear whether VEGFA directly contributes to HSC specification. This is an important question for our understanding of how HSCs are formed and for developing their production in vitro. Through knockdown of the regulator ETO2 in embryogenesis, we report a specific decrease in expression of medium/long Vegfa isoforms in somites. This leads to absence of Notch1 expression and failure of HSC specification in the dorsal aorta (DA), independently of vessel formation and arterial specification. Vegfa hypomorphs and isoform-specific (medium/long) morphants not only recapitulate this phenotype but also demonstrate that VEGFA short isoform is sufficient for DA development. Therefore, sequential, isoform-specific VEGFA signaling successively induces the endothelial, arterial, and HSC programs in the DA.

PubMed ID: 23318133
PMC ID: PMC3560039
Article link: Dev Cell
Grant support: [+]
Genes referenced: cbfa2t2 cbfa2t3 cd93 cfd dlc dll4 efnb2 etv6 fli1 flt1 flt4 gata2 gfi1 gja4 hba1 hba4 kdr lmo2 myb notch1 notch3 notch4 notch4.2 odc1 pecam1 ptch1 runx1 shh spib tal1 tbx2 tek vegfa
Morpholinos: cbfa2t3 MO2 cbfa2t3 MO3


Article Images: [+] show captions
References [+] :
Burns, Hematopoietic stem cell fate is established by the Notch-Runx pathway. 2005, Pubmed


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