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First published online 18 March 2009
doi: 10.1242/dev.032748
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1 Weatherall Institute of Molecular Medicine, University of Oxford, John
Radcliffe Hospital, Headington, Oxford OX3 9DS, UK.
2 The Victor Chang Cardiac Research Institute, Level 6, 384 Victoria Street,
Darlinghurst, Sydney, NSW 2010, Australia.
* Author for correspondence (e-mail: roger.patient{at}imm.ox.ac.uk)
Accepted 24 February 2009
Over the past few years it has become clear that over half of the mammalian heart derives from outside the heart field as originally defined. Such a second heart field, however, has not been described in zebrafish, which could explain its smaller, two-chambered heart. Instead, zebrafish have a population of haemangioblasts, which is absent in mammalian embryos, raising the possibility that these cells represent the evolutionary ancestor of the second heart field. Here, we show for the first time that the genetic programmes of these anterior haemangioblasts and the adjacent heart field are co-regulated, by transcription factors previously associated with heart but not blood or endothelial development. We demonstrate that gata4, gata5 and gata6 are essential for anterior haemangioblast specification, and for subsequent myelopoiesis, acting as early as cloche and upstream of scl. The requirement for gata4, gata5 and gata6 in myeloid, endothelial and cardiac specification is in the mesoderm, but these factors also control, from within the endoderm and the yolk syncytial layer, the migration of the cardiac precursors as they differentiate. This genetic link between the blood/endothelial and cardiac programmes supports the notion that this haemangioblast population in zebrafish is an evolutionary antecedent of the second heart field, and has implications for the differentiation of haemangioblasts and cardiomyocytes from pluripotent cells, and for the origins of stem cells in the adult heart.
Key words: Myelopoiesis, Cardiogenesis, GATA factors, Second heart field, Haemangioblasts, Transcriptional regulation, Evolution, Adult stem cells, Zebrafish
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