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The core-binding factor β subunit is required for bone formation and hematopoietic maturation

Nature Genetics volume 32, pages 645–649 (2002)Cite this article

Abstract

Core-binding factor β (Cbfβ) is the common non-DNA-binding subunit of the Cbf family of heterodimeric transcription factors. Mice deficient in Cbfβ have a severe block in fetal liver hematopoiesis at the stage of hematopoietic stem cell (HSC) emergence1,2. Here we show that by providing Cbfβ function in endothelial cells and hematopoietic progenitors we can rescue fetal liver hematopoiesis in Cbfβ-deficient embryos. The rescued mice die at birth, however, with severe defects in skeletal development, though intramembranous ossification occurs to some extent. Fetal liver hematopoiesis is restored at embryonic day (E) 12.5, but by E17.5 significant impairments in lymphopoiesis and myelopoiesis are observed. Thus, we conclude that the Cbfβ subunit is required for HSC emergence, bone formation and normal differentiation of lymphoid and myeloid lineage cells.

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Figure 1: The GFP/Cbfβ protein is expressed in endothelial cells and in fetal liver hematopoietic progenitors, but not in differentiated blood cells.
Figure 2: The Tek-GFP/Cbfb transgene rescues the mid-gestation embryonic lethality of Cbfβ deficient mice, but uncovers a requirement for Cbfβ in bone formation.
Figure 3: Hematopoiesis in Cbfb−/− Tg(Tek-GFP/Cbfb) fetuses is perturbed by E17.5.

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Acknowledgements

We thank A. Given, G. Ward, M. Kundu, M. de Bruijn, M. Binder, B. Trevant and S. Fiering for their advice and technical assistance, L. Karns for the Tek promoter and enhancer sequences and T. Sato for the Tg(Tek-GFP) mice. This work was supported by US Public Health Service grants to N.A.S., J.B.L. and G.S.S. and supported in part by the Core Grant of the Norris Cotton Cancer Center.

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Authors and Affiliations

  1. Department of Biochemistry, Dartmouth Medical School, Hanover, 03755, New Hampshire, USA

    Janelle Miller, Terryl Stacy & Nancy A. Speck

  2. Cartilage Biology and Orthopedics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA

    Alan Horner & Glen H. Nuckolls

  3. Departments of Medicine, Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire, USA

    Christopher Lowrey

  4. Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts, USA

    Jane B. Lian & Gary Stein

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Correspondence to Nancy A. Speck.

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Miller, J., Horner, A., Stacy, T. et al. The core-binding factor β subunit is required for bone formation and hematopoietic maturation. Nat Genet 32, 645–649 (2002). https://doi.org/10.1038/ng1049

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