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ER71 acts downstream of BMP, Notch, and Wnt signaling in blood and vessel progenitor specification.

FLK1-expressing (FLK1(+)) mesoderm generates blood and vessels. Here, we show that combined BMP, Notch, and Wnt signaling is necessary for efficient FLK1(+) mesoderm formation from embryonic stem cells (ESCs). Inhibition of BMP, Notch, and Wnt signaling pathways greatly decreased the generation of FLK1(+) mesoderm and expression of the Ets transcription factor Er71. Enforced expression of ER71 in ESCs resulted in a robust induction of FLK1(+) mesoderm; rescued the generation of FLK1(+) mesoderm when blocked by BMP, Notch, and Wnt inhibition; and enhanced hematopoietic and endothelial cell generation. Er71-deficient mice had greatly reduced FLK1 expression, died early in gestation, and displayed severe blood and vessel defects that are highly reminiscent of the Flk1 null mouse phenotype. Collectively, we provide compelling evidence that ER71 functions downstream of BMP, Notch, and Wnt signals and regulates FLK1(+) mesoderm, blood, and vessel development.

Pubmed ID: 18462699

Authors

  • Lee D
  • Park C
  • Lee H
  • Lugus JJ
  • Kim SH
  • Arentson E
  • Chung YS
  • Gomez G
  • Kyba M
  • Lin S
  • Janknecht R
  • Lim DS
  • Choi K

Journal

Cell stem cell

Publication Data

May 8, 2008

Associated Grants

  • Agency: NIDDK NIH HHS, Id: DK54508
  • Agency: NHLBI NIH HHS, Id: HL55337
  • Agency: NHLBI NIH HHS, Id: HL63736
  • Agency: NHLBI NIH HHS, Id: R01 HL055337
  • Agency: NHLBI NIH HHS, Id: R01 HL055337-13
  • Agency: NHLBI NIH HHS, Id: R01 HL063736
  • Agency: NHLBI NIH HHS, Id: R01 HL063736-09A1
  • Agency: NHLBI NIH HHS, Id: R01 HL081186

Mesh Terms

  • Animals
  • Blood Vessels
  • Bone Morphogenetic Protein 4
  • Cell Differentiation
  • Cell Lineage
  • Dipeptides
  • Endothelium, Vascular
  • Hematopoietic Stem Cells
  • Intercellular Signaling Peptides and Proteins
  • Male
  • Mesoderm
  • Mice
  • Mice, Knockout
  • Receptors, Notch
  • Signal Transduction
  • Stem Cells
  • Transcription Factors
  • Vascular Endothelial Growth Factor Receptor-2
  • Veratrum Alkaloids
  • Wnt Proteins