Transcription factor NF-E2 is required for platelet formation independent of the actions of thrombopoietin/MGDF in megakaryocyte development.
Despite the importance of blood platelets in health and disease, the mechanisms regulating their formation within megakaryocytes are unknown. We generated mice lacking the hematopoietic subunit (p45) of the heterodimeric erythroid transcription factor NF-E2. Unexpectedly, NF-E2-/- mice lack circulating platelets and die of hemorrhage; their megakaryocytes show no cytoplasmic platelet formation. Though platelets are absent, serum levels of the growth factor thrombopoietin/MGDF are not elevated above controls. Nonetheless, NF-E2-/- megakaryocytes proliferate in vivo in response to thrombopoietin administration. Thus, as an essential factor for megakaryocyte maturation and platelet production, NF-E2 must regulate critical target genes independent of the action of thrombopoietin. These findings provide insight into the genetic analysis of megakaryocyte maturation and thrombopoiesis.
Shivdasani
R A
RA
Division of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Rosenblatt
M F
MF
Zucker-Franklin
D
D
Jackson
C W
CW
Hunt
P
P
Saris
C J
CJ
Orkin
S H
SH
D000818:Animals; D001483:Base Sequence; D001773:Blood Cells / Q000166:cytology; D001792:Blood Platelets / Q000502:physiology*; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D004247:DNA / Q000032:analysis; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015672:Erythroid Precursor Cells / Q000473:pathology; D050981:Erythroid-Specific DNA-Binding Factors; D005786:Gene Expression Regulation; D008533:Megakaryocytes / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D050983:NF-E2 Transcription Factor; D050984:NF-E2 Transcription Factor, p45 Subunit; D016133:Polymerase Chain Reaction; D013921:Thrombocytopenia; D013926:Thrombopoietin / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D017931:DNA Primers; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050983:NF-E2 Transcription Factor; D050984:NF-E2 Transcription Factor, p45 Subunit; C494693:Nfe2 protein, mouse; D014157:Transcription Factors; D004247:DNA; D013926:Thrombopoietin