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 m echanisms regulating their formation within megakaryocytes are unknown . We generated mice lacking the hematopoietic subunit (p45) of the het erodimeric erythroid transcription factor NF-E2. Unexpectedly, NF-E2(- /-) mice lack circulating platelets and die of hemorrhage; their megak aryocytes 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 proli ferate in vivo in response to thrombopoietin administration. Thus, as an essential factor for megakaryocyte maturation and platelet producti on, NF-ES must regulate critical target genes independent of the actio n of thrombopoietin. These findings provide insight into the genetic a nalysis of megakaryocyte maturation and thrombopoiesis.