Estrogen defines the dorsal-ventral limit of VEGF regulation to specify the location of the hemogenic endothelial niche
Program in Gene Function and Expression
Cell and Developmental Biology | Cellular and Molecular Physiology | Genetics and Genomics
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 17beta-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.
DOI of Published Version
Carroll KJ, Esain V, Garnaas MK, Cortes M, Dovey MC, Nissim S, Frechette GM, Liu SY, Kwan W, Cutting CC, Harris JM, Gorelick DA, Halpern ME, Lawson ND, Goessling W, North TE. Estrogen defines the dorsal-ventral limit of VEGF regulation to specify the location of the hemogenic endothelial niche. Dev Cell. 2014 May 27;29(4):437-53. doi: 10.1016/j.devcel.2014.04.012. Link to article on publisher's site
Carroll, Kelli J.; Esain, Virginie; Garnaas, Maija K.; Cortes, Mauricio; Dovey, Michael C.; Nissim, Sahar; Frechette, Gregory M.; Liu, Sarah Y.; Kwan, Wanda; Cutting, Claire C.; Harris, James M.; Gorelick, Daniel A.; Halpern, Marnie E.; Lawson, Nathan D.; Goessling, Wolfram; and North, Trista E., "Estrogen defines the dorsal-ventral limit of VEGF regulation to specify the location of the hemogenic endothelial niche" (2014). Program in Gene Function and Expression Publications and Presentations. 246.