The core-binding factor beta subunit is required for bone formation and hematopoietic maturation.
Core-binding factor beta (Cbfbeta) is the common non-DNA-binding subunit of the Cbf family of heterodimeric transcription factors. Mice deficient in Cbfbeta have a severe block in fetal liver hematopoiesis at the stage of hematopoietic stem cell (HSC) emergence. Here we show that by providing Cbfbeta function in endothelial cells and hematopoietic progenitors we can rescue fetal liver hematopoiesis in Cbfbeta-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 Cbfbeta subunit is required for HSC emergence, bone formation and normal differentiation of lymphoid and myeloid lineage cells.
Miller
Janelle
J
Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA.
Horner
Alan
A
Stacy
Terryl
T
Lowrey
Christopher
C
Lian
Jane B
JB
Stein
Gary
G
Nuckolls
Glen H
GH
Speck
Nancy A
NA
D000818:Animals; D002454:Cell Differentiation; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005314:Embryonic and Fetal Development; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D005333:Fetus; D018507:Gene Expression Regulation, Developmental; D005804:Genes, Lethal; D005838:Genotype; D049452:Green Fluorescent Proteins; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology; D008099:Liver / Q000098:blood supply / Q000166:cytology / Q000502:physiology; D008164:Luminescent Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology; D010012:Osteogenesis; D011993:Recombinant Fusion Proteins / Q000502:physiology; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D004268:DNA-Binding Proteins; D008164:Luminescent Proteins; D011993:Recombinant Fusion Proteins; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D049452:Green Fluorescent Proteins