PUBLICATION
Estrogen defines the dorsal-ventral limit of VEGF regulation to specify the location of the hemogenic endothelial niche
- Authors
- 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.
- ID
- ZDB-PUB-170214-329
- 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
-
- Phenols/pharmacology
- Estradiol/analogs & derivatives
- Estradiol/pharmacology
- Proto-Oncogene Proteins/antagonists & inhibitors
- Proto-Oncogene Proteins/biosynthesis
- Basic Helix-Loop-Helix Transcription Factors/antagonists & inhibitors
- Basic Helix-Loop-Helix Transcription Factors/biosynthesis
- Ephrin-B2/antagonists & inhibitors
- Hemangioblasts/metabolism*
- Receptors, Estradiol/genetics
- Animals
- Estrogen Antagonists/pharmacology*
- Estrogens/pharmacology
- Signal Transduction
- Benzhydryl Compounds/pharmacology
- Ethinyl Estradiol/pharmacology
- Receptors, Notch/biosynthesis
- Heat-Shock Response
- Genistein/pharmacology
- Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors
- Core Binding Factor Alpha 2 Subunit/biosynthesis
- Vascular Endothelial Growth Factor A/antagonists & inhibitors
- Vascular Endothelial Growth Factor A/biosynthesis*
- Zebrafish/embryology*
- Zebrafish/genetics
- Morpholinos/genetics
- Hematopoietic Stem Cells/metabolism*
- Zebrafish Proteins/antagonists & inhibitors
- Zebrafish Proteins/biosynthesis*
- PubMed
- 24871948 Full text @ Dev. Cell
Citation
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. (2014) Estrogen defines the dorsal-ventral limit of VEGF regulation to specify the location of the hemogenic endothelial niche. Developmental Cell. 29:437-53.
Abstract
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 17?-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.
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Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
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Orthology
Engineered Foreign Genes
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