The formation of blood in the embryo is PAK1 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 display that BMP4 initially induces ventral-posterior (V-P) mesoderm and TNF-alpha inhibitor IC50 subsequently directs mesodermal cells towards 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 improvement, therefore placing BMP4 signaling upstream of your Cdx-Hox pathway. Wnt signaling cooperates in BMP-induced hemogenesis, and also the Wnt effector LEF1 mediates BMP4 activation of Cdx genes. Our information suggest that BMP signaling plays two distinct and sequential roles in the course of blood formation, at first as an inducer of mesoderm, and later to specify blood by means of activation of Wnt signaling as well as Cdx-Hox selleck chem Rho inhibitor pathway.