The oncogenic LIM-only transcription factor Lmo2 regulates angiogenesis but not vasculogenesis in mice

摘要

The LMO2 gene is activated by chromosomal translocations in human T cell acute leukemias, but in mouse embryogenesis, Lmo2 is essential for initiation of yolk sac and definitive hematopoiesis. The LMO2 protein comprises two LIM--zinc-finger-like protein in- teraction modules and functions by interaction with specific part- ners in DNA-binding transcription complexes. We have now inves- tigated the role of Lmo2-associated transcription complexes in the formation of the vascular system by following the fate of Lmo2- null embryonic stem (ES) cells in mouse chimeras. Lmo2 is ex- pressed in vascular endothelium, and Lmo2-null ES cells contrib- uted to the capillary network normally until around embryonic day 9. However, after this time, marked disorganization of the vascular system was observed in those chimeric mice that have a high contribution of Lmo2-null ES cells. Moreover, Lmo2-null ES cells do not contribute to endothelial cells of large vessel walls of surviving chimeric mice after embryonic day 10. These results show that Lmo2 is not needed for de novo capillary formation from meso- derm but is necessary for angiogenic remodeling of the existing capillary network into mature vasculature. Thus, Lmo2-mediated transcription complexes not only regulate distinct phases of he- matopoiesis but also angiogenesis, presumably by Lmo2 interact- ing with distinct partners in the different settings.