Its receptors, Flk1 and Flt1, are expressed on the hemangioblasts and angioblast, and Flt1 is expressed on the hematopoietic stem cells (HSCs) developing in the blood island ( Kabrun et al., 1997 Nishikawa et al., 1997 Choi, 2002). VEGFA plays a pivotal role in the first step of endothelial and hematopoietic development in the YS and at the onset of gastrulation is expressed in the YS visceral endoderm and mesothelium ( Damert et al., 2002). AML1-deficient mice die between E12–13 and fail to form definitive lineage hematopoiesis in the liver, but they have normal primitive YS erythropoiesis ( North et al., 2002 Mikkola and Orkin, 2002). CD41, possibly a direct target of SCL, is normally restricted to the megakaryocytic lineage in the adult, but in the YS it is expressed on multilineage definitive hematopoietic cells (but not on primitive erythroid lineage) and precedes the expression of the pan-lympho-hematopoietic marker CD45 ( Mikkola et al., 2003). SCL is a transcription factor whose inactivation leads to embryonic death at E9.5 because of the absence of red cells ( Gering et al., 1998). Moore, in Handbook of Stem Cells (Second Edition), 2013 Molecular Pathways Involved in Yolk Sac Hematopoietic Developmentīlood islands express: the vascular endothelial growth factor (VEGF) receptors Flk1 and Flt1 and the cytokine receptors cKit and cMpl the potential adhesion molecules CD34, CD41, CD44, PECAM-1, and VE-cadherin the transcription factors SCL/Tal-1, GATA1, GATA2, and AML1/Runx1 and transforming growth factor (TGF) family members TGFβ, BMP4, and their downstream signaling components – SMADs ( Baron 2001b Liu et al., 2003 Cantor and Orkin, 2002 Dickson et al., 1995).
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