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Novel Developmental Hemato-Vascular Endothelial Genes and Identification of Direct Genomic Targets of Ets Related Protein/Ets Variant 2 in Zebrafish


Seminal studies in the zebrafish mutant line cloche, which is embryonically lethal due to a deficiency in blood and vascular lineages, resulted in the identification of a critical transcription factor Ets Related Protein/ Ets Variant 2 (Etsrp/Etv2) that was necessary and sufficient for vasculogenesis and myelopoiesis. The mammalian homolog was subsequently identified and found to play functionally conserved roles. Because the forced expression of Etv2 alone is sufficient to ectopically induce vascular and myelopoietic genes, we interrogated the transcriptome of Etv2 overexpressing embryos with microarray and deep sequencing approaches and identified several novel vascular and myelopoietic genes downstream of Etv2 in zebrafish. Nevertheless, the number of genes directly induced by Etv2 to specify angioblasts from the lateral plate mesoderm, and the location of such binding would provide valuable information to understand how Etv2 regulates vasculogenesis and hematopoiesis. We therefore approached these questions with ChIP-sequencing and RNA-sequencing technologies to identify the direct genetic targets of Etv2 in zebrafish embryos. These datasets were independently validated, and will provide a framework from which to understand how Etv2 directs the genetic networks that initiate vasculogenesis and myelopoiesis in zebrafish.

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