title: Expression levels of endoglin distinctively identify hematopoietic and endothelial progeny at different stages of yolk sac hematopoiesis.
abstract: Endoglin (Eng), an ancillary receptor of the transforming growth factor beta (TGFβ) signaling pathway superfamily, has been well recognized for its important function in vascular development and angiogenesis since its discovery more than a decade ago. Recent studies show that this receptor is also critical for the emergence of blood during embryonic development, and that at E7.5, endoglin together with Flk-1 identifies early mesoderm progenitors that are endowed with hematopoietic and endothelial potential. These two lineages emerge in very close association during embryogenesis, and because they share the expression of the same surface markers, it has been difficult to distinguish the earliest hematopoietic from endothelial cells. Here, we evaluated the function of endoglin in hematopoiesis as development progresses past E7.5, and found that the hematopoietic and endothelial progenitors can be distinguished by the levels of endoglin in E9.5 yolk sacs. Whereas endothelial cells are Eng(bright), hematopoietic activity is primarily restricted to a subset of cells that display dim expression of endoglin (Eng(dim)). Molecular characterization of these subfractions showed that endoglin-mediated induction of hematopoiesis occurs in concert with BMP2/BMP4 signaling. This pathway is highly active in Eng(dim) cells but significantly downregulated in the Eng knockout. Taken together, our findings show an important function for endoglin in mediating BMP2/BMP4 signaling during yolk sac hematopoietic development and suggest that the levels of this receptor modulate TGFβ versus bone morphogenetic protein (BMP) signaling.
authors.affiliation: Department of Medicine, Lillehei Heart Institute, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Luciene
authors.initials: L
authors.lastname: Borges
authors.forename: Michelina
authors.initials: M
authors.lastname: Iacovino
authors.forename: Naoko
authors.initials: N
authors.lastname: Koyano-Nakagawa
authors.forename: June
authors.initials: J
authors.lastname: Baik
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Garry
authors.forename: Michael
authors.initials: M
authors.lastname: Kyba
authors.forename: Rita C R
authors.initials: RC
authors.lastname: Perlingeiro
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D000071063:Endoglin; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D015398:Signal Transduction; D013347:Subcellular Fractions / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D015017:Yolk Sac / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; D000071063:Endoglin; C502004:Eng protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D016212:Transforming Growth Factor beta; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Early hematopoiesis; Endoglin; Flk-1; Smad1/5/8; TGFβ/BMP signaling; Yolk sac