Differentiation of the mammalian hepatic primordiumin vitro:I. Morphogenesis and the onset of haematopoiesis

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Abstract
This study was made to determine the nature of tissue contributions to murine hepatic morphogenesis, the developmental potential in vitro of various hepatic regions prior to and during definitive liver development, and to accurately determine the time of onset of hepatic haematopoiesis in vitro. Embryos were precisely staged by somite counts as well as time of original mating, and tissues were removed from the hepatic area at stages between anterior intestinal portal (9 days gestation) and definitive foetal liver (11·75–12 days gestation), and maintained in vitro for up to 4 weeks. Explants of anterior intestinal portal origin gave rise only to sheets of epithelial cells, whereas tissues from embryos of 10–11 days gestation, containing the hepatic sacculation of the ventral wall of the gut, gave rise to sheets of polygonal, frequently binucleate cells and granule containing cells, both suggestive of hepatic cytodifferentiation. Sinusoidal morphogenesis was also observed. Haematopoiesis was detected in vitro only in explants from 11·5-to 12-day embryos (28 to 30+ somites). The blood elements observed consisted of erythroblasts, granulocytes, megakaryocytes as well as macrophages and yolk sac derived erythroblasts. Duct systems, probably representative of the bile system, were also observed to develop. Current theories regarding hepatic morphogenesis are considered in the light of these observations. The inductive and cell seeding concepts of the origin of haematopoietic cells are discussed in view of the observed precise timing of the onset of hepatic haematopoiesis. Due to the substantial gestation time-gap between the detection of possible circulating haematopoietic stem cells (9 days gestation) and the actual onset of hepatic haematopoiesis (11·5 days gestation), it is suggested that either a suitable microenvironment must first develop within the hepatic area for haematopoiesis to occur, or that haematopoietic tissue arises in situ in the hepatic Anlage.