Initiation of adult myelopoiesis can occur in the absence of c-Myb whereas subsequent development is strictly dependent on the transcription factor.
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 multilineage 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.
Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
R
R
Sumner
A
A
Crawford
M
M
Mucenski
J
J
Frampton
D000818:Animals; D002460:Cell Line; D005260:Female; D006801:Humans; D019891:Leukopoiesis / Q000502:physiology*; D008099:Liver / Q000196:embryology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology; D015017:Yolk Sac
D020598:Proto-Oncogene Proteins c-myb