BMP and Wnt Specify Hematopoietic Fate by Activation of the Cdx-Hox Pathway

Claudia Lengerke, Sabine Schmitt, Teresa V. Bowman, Il Ho Jang, Leila Maouche-Chretien, Shannon McKinney-Freeman, Alan J. Davidson, Matthias Hammerschmidt, Fabian Rentzsch, Jeremy B.A. Green, Leonard I. Zon, George Q. Daley

Research output: Contribution to journalArticle

155 Scopus citations

Abstract

The formation of blood in the embryo is dependent on bone morphogenetic protein (BMP), but how BMP signaling intersects with other regulators of hematopoietic development is unclear. Using embryonic stem (ES) cells, we show that BMP4 first induces ventral-posterior (V-P) mesoderm and subsequently directs mesodermal cells toward blood fate by activating Wnt3a and upregulating Cdx and Hox genes. When BMP signaling is blocked during this latter phase, enforced expression of either Cdx1 or Cdx4 rescues hematopoietic development, thereby placing BMP4 signaling upstream of the Cdx-Hox pathway. Wnt signaling cooperates in BMP-induced hemogenesis, and the Wnt effector LEF1 mediates BMP4 activation of Cdx genes. Our data suggest that BMP signaling plays two distinct and sequential roles during blood formation, initially as an inducer of mesoderm, and later to specify blood via activation of Wnt signaling and the Cdx-Hox pathway.

Original languageEnglish (US)
Pages (from-to)72-82
Number of pages11
JournalCell Stem Cell
Volume2
Issue number1
DOIs
StatePublished - Jan 10 2008
Externally publishedYes

Keywords

  • DEVBIO
  • STEMCELL

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

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    Lengerke, C., Schmitt, S., Bowman, T. V., Jang, I. H., Maouche-Chretien, L., McKinney-Freeman, S., Davidson, A. J., Hammerschmidt, M., Rentzsch, F., Green, J. B. A., Zon, L. I., & Daley, G. Q. (2008). BMP and Wnt Specify Hematopoietic Fate by Activation of the Cdx-Hox Pathway. Cell Stem Cell, 2(1), 72-82. https://doi.org/10.1016/j.stem.2007.10.022