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

The c-Myb transcriptional regulator is crucial to the development and funct ioning 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. BS analysing c-myb(-/-) chimaeras we show that no mature cells of any lymph oid or myeloid lineage can be detected in adult haemopoietic tissues. This demonstrates that the effects of c-myb ablation on haemopoiesis are cell au tonomous and correlates with an absence in the c-myb(-/-) foetal liver of u ni- and multilineage CFUs. Indeed, CFU assays performed on E8.5 yolk sac ce lls revealed that haemopoietic progenitors are already defective at this st -age. 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(-/-) d onor-derived CD34(+)/Kit(+) cells, representing committed definitive progen itors, initially populated the foetal liver, but are unable to expand like wild type progenitors. Our results showing no megakaryocytic CFUs and a red uction in the absolute numbers of megakargocytes in the c-myb(-/-) foetal l iver also refute early suggestions that megakaryopoiesis is unaffected by t he absence of c-Myb.