C Collart1, A Ciccarelli2, K Ivanovitch3, I Rosewell4, S Kumar2,5, G Kelly6, A Edwards7, J C Smith3. 1. Developmental Biology Laboratory, Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK. Clara.Collart@crick.ac.uk. 2. Advanced Light Microscopy Facility, Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK. 3. Developmental Biology Laboratory, Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK. 4. Genetic Modification Service, Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK. 5. Photonics Group, 606 Blackett Laboratory, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK. 6. Bioinformatics and Biostatistics Facility, Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK. 7. Advanced Sequencing Facility, Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.
Abstract
BACKGROUND: Vasculogenesis in amniotes is often viewed as two spatially and temporally distinct processes, occurring in the yolk sac and in the embryo. However, the spatial origins of the cells that form the primary intra-embryonic vasculature remain uncertain. In particular, do they obtain their haemato-endothelial cell fate in situ, or do they migrate from elsewhere? Recently developed imaging techniques, together with new Tal1 and existing Flk1 reporter mouse lines, have allowed us to investigate this question directly, by visualising cell trajectories live and in three dimensions. RESULTS: We describe the pathways that cells follow to form the primary embryonic circulatory system in the mouse embryo. In particular, we show that Tal1-positive cells migrate from within the yolk sac, at its distal border, to contribute to the endocardium, dorsal aortae and head vasculature. Other Tal1 positive cells, similarly activated within the yolk sac, contribute to the yolk sac vasculature. Using single-cell transcriptomics and our imaging, we identify VEGF and Apela as potential chemo-attractants that may regulate the migration into the embryo. The dorsal aortae and head vasculature are known sites of secondary haematopoiesis; given the common origins that we observe, we investigate whether this is also the case for the endocardium. We discover cells budding from the wall of the endocardium with high Tal1 expression and diminished Flk1 expression, indicative of an endothelial to haematopoietic transition. CONCLUSIONS: In contrast to the view that the yolk sac and embryonic circulatory systems form by two separate processes, our results indicate that Tal1-positive cells from the yolk sac contribute to both vascular systems. It may be that initial Tal1 activation in these cells is through a common mechanism.
BACKGROUND: Vasculogenesis in amniotes is often viewed as two spatially and temporally distinct processes, occurring in the yolk sac and in the embryo. However, the spatial origins of the cells that form the primary intra-embryonic vasculature remain uncertain. In particular, do they obtain their haemato-endothelial cell fate in situ, or do they migrate from elsewhere? Recently developed imaging techniques, together with new Tal1 and existing Flk1 reporter mouse lines, have allowed us to investigate this question directly, by visualising cell trajectories live and in three dimensions. RESULTS: We describe the pathways that cells follow to form the primary embryonic circulatory system in the mouse embryo. In particular, we show that Tal1-positive cells migrate from within the yolk sac, at its distal border, to contribute to the endocardium, dorsal aortae and head vasculature. Other Tal1 positive cells, similarly activated within the yolk sac, contribute to the yolk sac vasculature. Using single-cell transcriptomics and our imaging, we identify VEGF and Apela as potential chemo-attractants that may regulate the migration into the embryo. The dorsal aortae and head vasculature are known sites of secondary haematopoiesis; given the common origins that we observe, we investigate whether this is also the case for the endocardium. We discover cells budding from the wall of the endocardium with high Tal1 expression and diminished Flk1 expression, indicative of an endothelial to haematopoietic transition. CONCLUSIONS: In contrast to the view that the yolk sac and embryonic circulatory systems form by two separate processes, our results indicate that Tal1-positive cells from the yolk sac contribute to both vascular systems. It may be that initial Tal1 activation in these cells is through a common mechanism.
Authors: Michael J Ferkowicz; Mark Starr; Xiaodong Xie; Weiming Li; Scott A Johnson; William C Shelley; Paul R Morrison; Mervin C Yoder Journal: Development Date: 2003-09 Impact factor: 6.868
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Authors: Hedia Chagraoui; Maiken S Kristiansen; Juan Pablo Ruiz; Ana Serra-Barros; Johanna Richter; Elisa Hall-Ponselé; Nicki Gray; Dominic Waithe; Kevin Clark; Philip Hublitz; Emmanouela Repapi; Georg Otto; Paul Sopp; Stephen Taylor; Supat Thongjuea; Paresh Vyas; Catherine Porcher Journal: Nat Commun Date: 2018-12-18 Impact factor: 14.919