AN EARLY PRE-LIVER INTRA-EMBRYONIC SOURCE OF CFU-S IN THE DEVELOPING MOUSE

IT is widely accepted that during murine embryogenesis, totipotent hae matopoietic stem cells first originate in the yolk sac, then migrate t o the fetal liver and finally colonize the bone marrow shortly before birth1,2. This view is based on in vitro studies showing that yolk sac cells can differentiate into various haematopoietic lineages1,3-7 and in vivo studies showing that yolk sac contains spleen colony-forming units (CFU-S) beginning at day 8 of gestation1. However, some investig ators have failed to find statistically significant numbers of CFU-S a rising from day 9 yolk sac3,8-11 and, although one group reported that yolk sac could repopulate the haematopoietic system of W mutant mice2 , others have failed to confirm yolk sac-derived repopulation of adult s3,12. In the avian and amphibian systems, the yolk sac gives rise onl y to early, transitory haematopoiesis whereas the definitive adult hae matopoietic stem cells in these vertebrates are derived from the mesod ermal region containing the dorsal aorta13-17. Because this analogous area of the mouse embryo has not been previously examined for haematop oietic activity, we directly compared the CFU-S activity of the aorta, gonad, mesonephros (AGM) region with the yolk sac and fetal liver dur ing embryogenesis. Here we report that this intra-embryonic AGM region contains CFU-S activity at a higher frequency than that in embryonic yolk sac and that such activity appears in the AGM region before the f etal liver.