Figure 3.

Signaling factors involved in mammalian embryonic hematopoietic development. Initially, to form the stromal environment supportive of hematopoietic development, Nodal/bone morphogenic protein 4 (bmp4)/Wnt3a is required for patterning of the primitive streak. Once the stromal environment is established, sonic hedgehog (Shh) secreted by the notochord induces the production of vascular endothelial growth factor alpha (VEGFa) by stromal cells, which signal to activate the transcription of Notch1 in hematopoietic precursors. Notch1 signaling then induces the transcription of members of the Lim-domain-binding 1 (Ldb1) complex, which in turn induces the transcription of runt related protein 1 (Runx1). GATA2, GATA box binding protein 2; Lmo2, Lim-motif 2; Scl, stem cell leukemia; Wnt3a, wingless-type MMTV integration site family, member 3A.