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To program pluripotent cells into blood, a knowledge of the locations of precursors during their journey through the embryo and the signals they experience would be informative. The anterior (a) and posterior (p) ventral blood islands (VBIs) in Xenopus are derived from opposite sides of the pregastrula embryo. The aVBI goes through a "hemangioblast" state, characterized by coexpression of blood and endothelial genes at neurula stages, whereas the pVBI expresses these genes in a nonoverlapping fashion several hours later, after commitment to either a blood or an endothelial fate. We describe a novel role for fibroblast growth factor (FGF) in controlling the timing of Scl, Lmo2, and Runx1 expression in the 2 VBI compartments. Blocking FGF signaling during gastrulation expands expression at neurula stages into posterior regions. We show, by lineage labeling, explant analysis, and targeted blocking of FGF signaling, that this is due to the pVBI prematurely expressing these genes with the timing of the aVBI. In contrast, overexpression of FGF in aVBI precursors eliminates the anterior hemangioblast program. Using this information, we have recapitulated the anterior hemangioblast program in pluripotent cells in vitro by inhibiting FGF signaling in anterior mesoderm induced by activin and exposed to bone morphogenetic protein (BMP) signaling.

Original publication

DOI

10.1182/blood-2007-03-081323

Type

Journal article

Journal

Blood

Publication Date

01/02/2008

Volume

111

Pages

1157 - 1166

Keywords

Animals, Biomimetic Materials, Blood Cells, Bone Morphogenetic Proteins, Cell Differentiation, Core Binding Factor Alpha 2 Subunit, DNA-Binding Proteins, Fibroblast Growth Factors, Gastrointestinal Tract, Gene Expression Regulation, Developmental, In Vitro Techniques, Intracellular Signaling Peptides and Proteins, Metalloproteins, Proto-Oncogene Proteins, Pyrroles, Receptors, Fibroblast Growth Factor, Signal Transduction, Transcription Factors, Xenopus Proteins, Xenopus laevis