ZFIN ID: ZDB-PUB-170214-329
Estrogen defines the dorsal-ventral limit of VEGF regulation to specify the location of the hemogenic endothelial niche
Carroll, K.J., Esain, V., Garnaas, M.K., Cortes, M., Dovey, M.C., Nissim, S., Frechette, G.M., Liu, S.Y., Kwan, W., Cutting, C.C., Harris, J.M., Gorelick, D.A., Halpern, M.E., Lawson, N.D., Goessling, W., North, T.E.
Date: 2014
Source: Developmental Cell   29: 437-53 (Journal)
Registered Authors: Cutting, Claire, Dovey, Michael, Garnaas, Maija, Goessling, Wolfram, Gorelick, Daniel, Halpern, Marnie E., Harris, James, Lawson, Nathan, Nissim, Sahar, North, Trista
Keywords: none
MeSH Terms:
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors/antagonists & inhibitors
  • Basic Helix-Loop-Helix Transcription Factors/biosynthesis
  • Benzhydryl Compounds/pharmacology
  • Core Binding Factor Alpha 2 Subunit/biosynthesis
  • Ephrin-B2/antagonists & inhibitors
  • Estradiol/analogs & derivatives
  • Estradiol/pharmacology
  • Estrogen Antagonists/pharmacology*
  • Estrogens/pharmacology
  • Ethinyl Estradiol/pharmacology
  • Genistein/pharmacology
  • Heat-Shock Response
  • Hemangioblasts/metabolism*
  • Hematopoietic Stem Cells/metabolism*
  • Morpholinos/genetics
  • Phenols/pharmacology
  • Proto-Oncogene Proteins/antagonists & inhibitors
  • Proto-Oncogene Proteins/biosynthesis
  • Receptors, Estradiol/genetics
  • Receptors, Notch/biosynthesis
  • Signal Transduction
  • Vascular Endothelial Growth Factor A/antagonists & inhibitors
  • Vascular Endothelial Growth Factor A/biosynthesis*
  • Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish Proteins/antagonists & inhibitors
  • Zebrafish Proteins/biosynthesis*
PubMed: 24871948 Full text @ Dev. Cell
Genetic control of hematopoietic stem and progenitor cell (HSPC) function is increasingly understood; however, less is known about the interactions specifying the embryonic hematopoietic niche. Here, we report that 17β-estradiol (E2) influences production of runx1+ HSPCs in the AGM region by antagonizing VEGF signaling and subsequent assignment of hemogenic endothelial (HE) identity. Exposure to exogenous E2 during vascular niche development significantly disrupted flk1+ vessel maturation, ephrinB2+ arterial identity, and specification of scl+ HE by decreasing expression of VEGFAa and downstream arterial Notch-pathway components; heat shock induction of VEGFAa/Notch rescued E2-mediated hematovascular defects. Conversely, repression of endogenous E2 activity increased somitic VEGF expression and vascular target regulation, shifting assignment of arterial/venous fate and HE localization; blocking E2 signaling allowed venous production of scl+/runx1+ cells, independent of arterial identity acquisition. Together, these data suggest that yolk-derived E2 sets the ventral boundary of hemogenic vascular niche specification by antagonizing the dorsal-ventral regulatory limits of VEGF.