Submitted March 23, 2007
Accepted October 6, 2007
FGF controls the timing of Scl, Lmo2 and Runx1 expression during embryonic blood development
Maggie Walmsley, David Cleaver, and Roger Patient*
MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford University, Oxford, Oxon, United Kingdom
* Corresponding author; email: roger.patient{at}imm.ox.ac.uk.
To programme 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 (VBI) in Xenopus are derived from opposite sides of the pre-gastrula embryo. The aVBI goes through a 'haemangioblast' state, characterised by co-expression of blood and endothelial genes at neurula stages, whereas the pVBI expresses these genes in a non-overlapping fashion several hours later, after commitment to either a blood or an endothelial fate. Here we describe a novel role for FGF in controlling the timing of Scl, Lmo2 and Runx1 expression in the two VBI compartments. Blocking FGF signaling during gastrulation expands expression at neurula stages into posterior regions. We show by lineage labelling, 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, over expression of FGF in aVBI precursors eliminates the anterior haemangioblast programme. Using this information, we have recapitulated the anterior haemangioblast programme in pluripotent cells in vitro by inhibiting FGF signaling in anterior mesoderm induced by activin and exposed to BMP signaling.
