The transcription factor c-Myc regulates the expression of numerous genes involved in many aspects of cellular function and its deregulation is associated with a wide range of human tumours. However, the physiological role of c-Myc during development is poorly understood. Now, two papers in this issue suggest that c-Myc functions primarily in haematopoiesis during mammalian development. First, on , Rong Wang and colleagues report that c-Myc expression in the haematopoietic lineage indirectly controls angiogenesis (the growth of new blood vessels from pre-existing vessels). c-myc-null mouse embryos, which die by embryonic day (E) 10.5, have many severe developmental abnormalities,including a lack of elaborate blood vessels. To study the role of c-Myc in vascular development, the researchers deleted the c-myc gene in selected cell lineages using Cre-lox-mediated recombination. To their surprise, the elimination of c-Myc in most endothelial cells in mouse embryos did not abrogate the de novo differentiation of endothelial cells(vasculogenesis) or their proliferation, survival and migration. The mutant embryos also survived to beyond E12.5. By contrast, the elimination of c-Myc in haematopoietic lineages alone caused defects in both haematopoiesis and angiogenesis, suggesting that hematopoietic defects can disrupt angiogenesis. Further insights into the role of c-myc during development are also provided by Andreas Trumpp and colleagues on , who show that the severe abnormalities previously seen in c-myc-null embryos are largely absent when c-myc is eliminated specifically in the epiblast, which suggests that the c-myc-null mutant phenotype results mainly from placental insufficiency. Although the epiblast-restricted c-Myc deficient embryos, which express c-Myc in placental but not in embryonic cells, appear surprisingly normal, they still die around E12, the researchers report. Specifically, these embryos have non-functional haematopoietic stem cells, are anaemic because of apoptosis of erythrocyte precursors, and have defective livers. Interestingly, the elimination of c-Myc in the hepatoblast lineage alone did not affect liver or haematopoietic development, but the elimination of c-Myc in the haematopoietic lineage affected both liver and blood development. Thus, both these papers unexpectedly show that c-Myc function is not required ubiquitously during development, but instead is specifically essential for haematopoiesis, which then supports vascular and liver development.
