Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Haemangioblast commitment is initiated in the primitive streak of the mouse embryo


Haematopoietic and vascular cells are thought to arise from a common progenitor called the haemangioblast. Support for this concept has been provided by embryonic stem (ES) cell differentiation studies that identified the blast colony-forming cell (BL-CFC), a progenitor with both haematopoietic and vascular potential1,2. Using conditions that support the growth of BL-CFCs, we identify comparable progenitors that can form blast cell colonies (displaying haematopoietic and vascular potential) in gastrulating mouse embryos. Cell mixing and limiting dilution analyses provide evidence that these colonies are clonal, indicating that they develop from a progenitor with haemangioblast potential. Embryo-derived haemangioblasts are first detected at the mid-streak stage of gastrulation and peak in number during the neural plate stage. Analysis of embryos carrying complementary DNA of the green fluorescent protein targeted to the brachyury locus demonstrates that the haemangioblast is a subpopulation of mesoderm that co-expresses brachyury (also known as T) and Flk-1 (also known as Kdr). Detailed mapping studies reveal that haemangioblasts are found at highest frequency in the posterior region of the primitive streak, indicating that initial stages of haematopoietic and vascular commitment occur before blood island development in the yolk sac.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Characteristics and cell lineage potentials of the mouse haemangioblast.
Figure 2: Clonality of haemangioblast-derived colonies and kinetics of haemangioblast development.
Figure 3: Isolation and characterization of GFP- and Flk-1-expressing cell populations from E7.5 GFP–Bry+/- embryos.
Figure 4: Localization of the haemangioblast in the embryo.


  1. Choi, K., Kennedy, M., Kazarov, A., Papadimitriou, J. C. & Keller, G. A common precursor for hematopoietic and endothelial cells. Development 125, 725–732 (1998)

    CAS  PubMed  Google Scholar 

  2. Kennedy, M. et al. A common precursor for primitive and definitive hematopoiesis. Nature 386, 488–493 (1997)

    Article  CAS  Google Scholar 

  3. Millauer, B. et al. High affinity VEGF binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis. Cell 72, 835–846 (1993)

    Article  CAS  Google Scholar 

  4. Yamaguchi, T. P., Dumont, D. J., Conlon, R. A., Breitman, M. L. & Rossant, J. flk-1, an flt-related receptor tyrosine kinase is an early marker for endothelial cell precursors. Development 118, 489–498 (1993)

    CAS  PubMed  Google Scholar 

  5. Kabrun, N. et al. Flk-1 expression defines a population of early embryonic hematopoietic precursors. Development 124, 2039–2048 (1997)

    CAS  PubMed  Google Scholar 

  6. Kallianpur, A. R., Jordan, J. E. & Brandt, S. J. The SCL/TAL-1 gene is expressed in progenitors of both the hematopoietic and vascular systems during embryogenesis. Blood 83, 1200–1208 (1994)

    CAS  PubMed  Google Scholar 

  7. Silver, L. & Palis, J. Initiation of murine embryonic erythropoiesis: a spatial analysis. Blood 89, 1154–1164 (1997)

    CAS  PubMed  Google Scholar 

  8. Breier, G. et al. Molecular cloning and expression of murine vascular endothelial-cadherin in early stage development of cardiovascular system. Blood 87, 630–641 (1996)

    CAS  PubMed  Google Scholar 

  9. Orkin, S. H. GATA-binding transcription factors in hematopoietic cells. Blood 80, 575–581 (1992)

    CAS  PubMed  Google Scholar 

  10. Robertson, S. M., Kennedy, M., Shannon, J. M. & Keller, G. A transitional stage in the commitment of mesoderm to hematopoiesis requiring the transcription factor SCL/tal-1. Development 127, 2447–2459 (2000)

    CAS  PubMed  Google Scholar 

  11. Wilkinson, D. G., Bhatt, S. & Herrmann, B. G. Expression pattern of the mouse T gene and its role in mesoderm formation. Nature 343, 657–659 (1990)

    Article  CAS  Google Scholar 

  12. Lyons, I. et al. Myogenic and morphogenetic defects in the heart tubes of murine embryos lacking the homeo box gene Nkx2–5. Genes Dev. 9, 1654–1666 (1995)

    Article  CAS  Google Scholar 

  13. Sitzmann, J., Noben-Trauth, K. & Klempnauer, K.-H. Expression of mouse c-myb during embryonic development. Oncogene 11, 2273–2279 (1995)

    CAS  PubMed  Google Scholar 

  14. Zhang, J. C. et al. Analysis of SM22alpha-deficient mice reveals unanticipated insights into smooth muscle cell differentiation and function. Mol. Cell. Biol. 21, 1336–1344 (2001)

    Article  CAS  Google Scholar 

  15. Duband, J. L., Gimona, M., Scatena, M., Sartore, S. & Small, J. V. Calponin and SM 22 as differentiation markers of smooth muscle: spatiotemporal distribution during avian embryonic development. Differentiation 55, 1–11 (1993)

    Article  CAS  Google Scholar 

  16. Ema, M. et al. Combinatorial effects of Flk1 and Tal1 on vascular and hematopoietic development in the mouse. Genes Dev. 17, 380–393 (2003)

    Article  CAS  Google Scholar 

  17. Fehling, H. J. et al. Tracking mesoderm induction and its specification to the hemangioblast during embryonic stem cell differentiation. Development 130, 4217–4227 (2003)

    Article  CAS  Google Scholar 

  18. Herrmann, B. G. Expression pattern of the Brachyury gene in whole-mount TWis/TWis mutant embryos. Development 113, 913–917 (1991)

    CAS  PubMed  Google Scholar 

  19. Biben, C. et al. Murine cerberus homologue mCer-1: a candidate anterior patterning molecule. Dev. Biol. 194, 135–151 (1998)

    Article  CAS  Google Scholar 

  20. Belo, J. A. et al. Cerberus-like is a secreted factor with neutralizing activity expressed in the anterior primitive endoderm of the mouse gastrula. Mech. Dev. 68, 45–57 (1997)

    Article  CAS  Google Scholar 

  21. Saga, Y. et al. MesP1: a novel basic helix-loop-helix protein expressed in the nascent mesodermal cells during mouse gastrulation. Development 122, 2769–2778 (1996)

    CAS  PubMed  Google Scholar 

  22. Shalaby, F. et al. A requirement for Flk1 in primitive and definitive hematopoiesis and vasculogenesis. Cell 89, 981–990 (1997)

    Article  CAS  Google Scholar 

  23. Kinder, S. J. et al. The orderly allocation of mesodermal cells to the extraembryonic structures and the anteroposterior axis during gastrulation of the mouse embryo. Development 126, 4691–4701 (1999)

    CAS  PubMed  Google Scholar 

  24. Cumano, A., Dieterlen-Lièvre, F. & Godin, I. Lymphoid potential, probed before circulation in mouse is restricted to caudal intraembryonic splanchnopleura. Cell 86, 907–916 (1996)

    Article  CAS  Google Scholar 

  25. Cumano, A., Ferraz, J., Klaine, M., Di Santo, J. & Godin, I. Intraembryonic, but not yolk sac hematopoietic precursors, isolated before circulation, provide long-term multilineage reconstitution. Immunity 15, 477–485 (2001)

    Article  CAS  Google Scholar 

  26. Palis, J., Roberston, S., Kennedy, M., Wall, C. & Keller, G. Development of erythroid and myeloid progenitors in the yolk sac and embryo proper of the mouse. Development 126, 5073–5084 (1999)

    CAS  PubMed  Google Scholar 

  27. Downs, K. M. & Davies, T. Staging of gastrulating mouse embryos by morphological landmarks in the dissecting microscope. Development 118, 1255–1266 (1993)

    CAS  PubMed  Google Scholar 

  28. Brady, G. & Iscove, N. N. Construction of cDNA libraries from single cells. Methods Enzymol. 225, 611–623 (1993)

    Article  CAS  Google Scholar 

Download references


We thank P. Gadue, S. Irion and S. Kattman for critical reading of this manuscript. We also thank the Mount Sinai Flow Cytometry Shared Research Facility for sorting assistance. This work was supported by NIH grants (G.K. and J.P.). H.J.F. is supported by grants from a Sonderforschungsbereich (SFB) and the IZKF Ulm.

Author information

Authors and Affiliations


Corresponding authors

Correspondence to James Palis or Gordon Keller.

Ethics declarations

Competing interests

The authors declare that they have no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Huber, T., Kouskoff, V., Joerg Fehling, H. et al. Haemangioblast commitment is initiated in the primitive streak of the mouse embryo. Nature 432, 625–630 (2004).

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI:

This article is cited by


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing