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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.

Original publication

DOI

10.1016/j.devcel.2012.12.004

Type

Journal article

Journal

Dev Cell

Publication Date

28/01/2013

Volume

24

Pages

144 - 158

Keywords

Animals, Aorta, Arteries, Co-Repressor Proteins, Embryonic Development, Endothelial Cells, Endothelium, Vascular, Hematopoiesis, Hematopoietic Stem Cells, Morpholinos, Nuclear Proteins, Protein Isoforms, Receptor, Notch1, Signal Transduction, Transcription Factors, Transcription, Genetic, Vascular Endothelial Growth Factor A, Xenopus Proteins, Xenopus laevis