Nature Genetics32, 645 - 649 (2002)
Published online: 18 November 2002; | doi:10.1038/ng1049
The core-binding factor subunit is required for bone formation and hematopoietic maturation
Janelle Miller1, Alan Horner2, Terryl Stacy1, Christopher Lowrey3, Jane B. Lian4, Gary Stein4, Glen H. Nuckolls2
& Nancy A. Speck1
1
Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA.
2
Cartilage Biology and Orthopedics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
3
Departments of Medicine, Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire, USA.
4
Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Core-binding factor (Cbf) is the common non-DNA-binding subunit of the Cbf family of heterodimeric transcription factors. Mice deficient in Cbf have a severe block in fetal liver hematopoiesis at the stage of hematopoietic stem cell (HSC) emergence1,
2. Here we show that by providing Cbf function in endothelial cells and hematopoietic progenitors we can rescue fetal liver hematopoiesis in Cbf-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 Cbf subunit is required for HSC emergence, bone formation and normal differentiation of lymphoid and myeloid lineage cells.
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