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A survey of mouse gene knockouts, transgene insertions and spontaneous mutations that are lethal prenatally reveals that surprisingly few developmental disturbances lead to death of the embryo and early foetus. These disturbances include failure to establish and maintain a vascular circulation, and failure to make the transition from yolk-sac-based to liver-based haematopoiesis. The embryo must also establish gestation-dependent routes of nutritional interaction with the mother, including implantation, formation of a yolk-sac vascular circulation, and formation of a chorioallantoic placenta. A number of embryonic organ and body systems, including the central nervous system, gut, lungs, urogenital system and musculoskeletal system, appear to have little or no survival value in utero.