Transcription factor that play a central role in proper axial mesendoderm morphogenesis and endoderm formation. Required for efficient differentiation of cells from the primitive streak stage to blood, by acting early in the recruitment and/or expansion of mesodermal progenitors to the hemangioblastic and hematopoietic lineages. Also involved in the morphogenesis of the heart and the gut during embryogenesis. Acts as a negative regulator of brachyury expression. Expressed in the primitive streak of the gastrulating embryo, and marks cells destined to form mesoderm and endoderm. Present in differentiating embryonic stem cells (at protein level). Initially expressed in visceral endoderm and becomes restricted to primitive streak and nascent mesoderm at gastrulation. This includes the hemangioblast, a precursor of hematopoietic and vascular stem cells. At 5.5 dpc, it is expressed symmetrically in the visceral endoderm but by 6.0 dpc this expression is noticeably asymmetric. At 6.5 dpc, expression is restricted to the nascent primitive streak and persists in the primitive streak through 7.5-9.5 dpc, marking those cells fated to form extra-embryonic and lateral mesoderm. By TGF-beta. Regulated by Nodal in mesendoderm morphogenesis. Regulated by FOXH1, which acts as a negative regulator by recruiting GSC to promoter during early development. Mice display defects in mesendoderm morphogenesis and patterning during development. Embryos show a marked thickening of the primitive streak. By the early somite stage, embryonic development is arrested, with the formation of abnormal head folds, foreshortened body axis, absence of heart tube and gut, deficient paraxial mesoderm, and an enlarged midline tissue mass that replaces the notochord. Development of extra-embryonic structures is generally normal except that the allantois is often disproportionately large for the size of the mutant embryo. Belongs to the paired homeobox family.