Wnt, activin, and BMP signaling regulate distinct stages in the developmental pathway from embryonic stem cells to blood

Cell Stem Cell. 2008 Jan 10;2(1):60-71. doi: 10.1016/j.stem.2007.10.011.


The embryonic stem cell differentiation system was used to define the roles of the Activin/Nodal, BMP, and canonical Wnt signaling pathways at three distinct developmental stages during hematopoietic ontogeny: induction of a primitive streak-like population, formation of Flk1(+) mesoderm, and induction of hematopoietic progenitors. Activin/Nodal and Wnt, but not BMP, signaling are required for the induction of the primitive streak. Although BMP is not required for primitive streak induction, it displays a strong posteriorizing effect on this population. All three signaling pathways regulate induction of Flk1(+) mesoderm. The specification of Flk1(+) mesoderm to the hematopoietic lineages requires VEGF and Wnt, but not BMP or Activin/Nodal signaling. Specifically, Wnt signaling is essential for commitment of the primitive erythroid, but not the definitive lineages. These findings highlight dynamic changes in signaling requirements during blood cell development and identify a role for Wnt signaling in the establishment of the primitive erythroid lineage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activins / physiology*
  • Animals
  • Bone Morphogenetic Protein 4 / physiology*
  • Cell Differentiation*
  • Cell Lineage*
  • Embryonic Induction
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / physiology*
  • Gene Expression Regulation, Developmental*
  • Hematopoiesis
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / physiology*
  • Mice
  • Primitive Streak / cytology
  • Primitive Streak / physiology
  • Signal Transduction*
  • Wnt Proteins / physiology*


  • Bmp4 protein, mouse
  • Bone Morphogenetic Protein 4
  • Wnt Proteins
  • activin A
  • Activins