Initiation of adult myelopoiesis can occur in the absence of c-Myb whereas subsequent development is strictly dependent on the transcription factor

Abstract

The c-Myb transcriptional regulator is crucial to the development and functioning of haemopoietic cells, so much so that mouse embryos homozygous for an inactivated c-myb allele die from anaemia at about day 15 of gestation. By analysing c-myb^−/− chimaeras we show that no mature cells of any lymphoid or myeloid lineage can be detected in adult haemopoietic tissues. This demonstrates that the effects of c-myb ablation on haemopoiesis are cell autonomous and correlates with an absence in the c-myb^−/− foetal liver of uni- and multi-lineage CFUs. Indeed, CFU assays performed on E8.5 yolk sac cells revealed that haemopoietic progenitors are already defective at this stage. However, although cells expressing high levels of c-Kit were absent, we could detect a high proportion of CD34⁺CD45⁺ cells in the c-myb^−/− foetal liver. Examination of chimaeric embryos revealed that c-myb^−/− donor-derived CD34⁺/Kit⁺ cells, representing committed definitive progenitors, initially populated the foetal liver, but are unable to expand like wild type progenitors. Our results showing no megakaryocytic CFUs and a reduction in the absolute numbers of megakaryocytes in the c-myb^−/− foetal liver also refute early suggestions that megakaryopoiesis is unaffected by the absence of c-Myb.